ESMO 2026 Trial Results & Physician Discussion

6-Another big finding from #ESMO26! A personalized mRNA cancer vaccine + pembrolizumab reduced the risk of melanoma recurrence or death by 42% (HR 0.58) in the phase 3 INTerpath-001 trial (1,137 patients). Interestingly, the benefit was more pronounced after 6 months (HR 0.42). Full paper accepted by NEJM, not yet published.

INTerpath-001: In macroscopic stage III melanoma, added value beyond neoadjuvant IO remains unclear. Next: target patients without MPR—but can vaccines overcome IO resistance? Value in stage IIB/IIC remains distinct. #ESMO26 @Larvol @OncoAlert @myESMO https://t.co/E4nKMmpxfy

🚨 #ESMO26 | INTerpath-001: Personalized mRNA neoantigen vaccine (intismeran) + pembrolizumab vs placebo + pembrolizumab in resected stage IIB–IV melanoma 💉 ✅ 2-yr RFS: 82.2% vs 70.0% ✅ 2-yr DMFS: 88.5% vs 80.2% ⚠️OS immature #Melanoma #OncTwitter #medX #MedTwitter https://t.co/XsCICLuf1D

🦉 Cancer Immunotherapy: A Week of Breakthroughs, Setbacks and New Biological Insights October 17–24, 2026 This week brought two major clinical advances: a personalized mRNA cancer vaccine significantly reduced melanoma recurrence, while a T-cell engager sharply extended survival in aggressive lung cancer. Other studies revealed why CAR-T cell quality, antigen presentation, and the tumor microenvironment can matter as much as immune activation itself. 🩸 1. A Personalized Cancer Vaccine Passes Its Biggest Test Moderna and Merck's individualized mRNA vaccine, intismeran autogene, reduced melanoma recurrence or death by 42% when combined with pembrolizumab in the Phase 3 INTerpath-001 trial. Among 1,137 patients with resected stage IIB–IV melanoma, two-year recurrence-free survival reached 82.2% versus 70.0% with pembrolizumab alone. Distant metastasis or death risk fell 38%, without a substantial increase in severe treatment-related toxicity. The results provide major randomized evidence that vaccines targeting patient-specific tumor mutations can improve clinical outcomes, not merely generate immune responses. Overall-survival data remain immature, and personalized manufacturing presents practical challenges. Source: https://t.co/FHlL1f9wPs 🩸 2. T-Cell Engagers Nearly Double Survival in Lung Cancer The Phase 3 DeLLphi-305 trial showed that adding Amgen's DLL3-targeted T-cell engager tarlatamab to durvalumab maintenance therapy extended median survival from 12.7 to 21.1 months in extensive-stage small-cell lung cancer. Among 563 patients, the combination reduced mortality risk by 58% and increased progression-free survival from 1.9 to 7.4 months. Tarlatamab recruits T cells directly to cancer cells, complementing durvalumab's PD-L1 blockade. The survival advantage is substantial, but cytokine-release syndrome occurred in 49.6% of patients, predominantly grade 1–2. Grade ≥3 treatment-related adverse events affected 20.9% versus 10.8%. These results could reshape first-line maintenance treatment, subject to regulatory review. Source: https://t.co/1TRq9VtseZ 🩸 3. Bladder Cancer Treatment Takes a Major Step Forward The Phase 3 VOLGA trial demonstrated a significant survival advantage with enfortumab vedotin plus durvalumab in patients with muscle-invasive bladder cancer unable or unwilling to receive cisplatin. Among 462 patients, the combination reduced the risk of progression, recurrence or death-related events by 49%. Two-year event-free survival reached 64% versus 45%, while overall survival was 78% versus 69%. The strategy combines targeted cytotoxic delivery through an antibody–drug conjugate with PD-L1 checkpoint inhibition. However, grade 3–4 adverse events occurred in 64% versus 44%. The results support a new perioperative option, although comparisons with other modern regimens remain unavailable. Source: https://t.co/VLXeYEzs9O 🩸 4. CAR-T Quality May Matter More Than Expansion A multicenter study involving 783 lymphoma patients found that CAR-T products enriched in naïve-like CCR7⁺CD45RA⁺ T cells were associated with significantly longer progression-free survival. In the primary cohort of 580 patients receiving axi-cel, these cells predicted better outcomes (HR 0.46; p=9.8×10⁻⁵), independently of tumor burden, inflammation and CAR-T expansion. An additional 203 patients confirmed the association. More previous treatment lines were linked to fewer naïve-like cells. The implication challenges a familiar assumption: expanding more CAR-T cells may be less important than preserving cells capable of sustained antitumor activity. Whether manufacturing changes that enrich these populations actually improve survival remains unproven. Source: https://t.co/GAN67wP3OV 🩸 5. A New Approach to Severe Immunotherapy Toxicity Researchers in Germany and Switzerland reported promising results using extracorporeal photopheresis to treat severe immune-related complications resistant to corticosteroids. The technique treats collected immune cells with a photosensitizing agent and ultraviolet light before returning them to circulation. In a prospective Phase 1b/2 study involving 30 patients, the response rate among evaluable inflammatory complications reached 96.3%, including responses in colitis, hepatitis and dermatitis. Treatment reduced inflammatory T-cell activity, including granzyme expression and interferon-γ/TNF signaling. No treatment-related serious adverse events occurred. The potential advantage is controlling dangerous inflammation without escalating systemic immunosuppression. However, the uncontrolled study cannot establish comparative efficacy or confirm preservation of antitumor immunity. Source: https://t.co/xDE6iBNXhy 🩸 6. Selective T-Cell Activation Shows Activity in Resistant Tumors Invikafusp alfa, an experimental bispecific antibody, activates selected T-cell populations expressing Vβ6 or Vβ10 T-cell receptors rather than broadly stimulating the immune system. In the Phase 1/2 START-001 trial, 4 of 27 patients (14.8%) treated at biologically optimal doses achieved objective responses, while 59.3% experienced disease control. Responses included microsatellite-stable colorectal cancer and PD-L1-negative lung cancer, where conventional checkpoint inhibition often has limited efficacy. The treatment expanded memory-like target T cells without broadly activating unrelated populations. This demonstrates preliminary clinical activity, not established benefit. Patient numbers remain small, durability is uncertain, and cytokine-release syndrome remains a risk. Source: https://t.co/2KupIGrKnT 🩸 7. Strong Vaccine Immunity Fails to Improve Pancreatic Cancer Outcomes The randomized Phase 2 AMPLIFY-7P trial tested camupepimut (ELI-002 7P), an off-the-shelf vaccine targeting mutant KRAS, in 144 patients with pancreatic cancer after standard treatment. Despite vaccine-specific T-cell responses in 98.9% of evaluable patients, the primary disease-free survival endpoint was missed: 23.8 versus 21.2 months (HR 0.85; p=0.5329). Subgroup analyses suggested possible benefit in patients without detectable circulating tumor DNA (HR 0.51) or prior radiotherapy (HR 0.59). The contrast is striking: nearly universal immune activation did not translate into a significant overall clinical benefit. Vaccination may work better against minimal residual disease, but subgroup signals remain exploratory and clinical efficacy is unproven. Source: https://t.co/18SHt23Nqc 🩸 8. Dual Checkpoint Blockade Targets Difficult Biliary Cancers Chinese investigators reported Phase 2 results for cadonilimab, a bispecific antibody blocking PD-1 and CTLA-4, combined with gemcitabine and cisplatin in advanced biliary tract cancer. Among 61 patients, the objective response rate reached 55.7%, with disease control in 85.2%. Median progression-free survival was 8.0 months and overall survival 15.6 months. Dual checkpoint blockade could provide broader immune activation than PD-1/PD-L1 inhibition alone. However, grade ≥3 adverse events occurred in 68.9%, including severe immune-related events in 18%. The single-arm design cannot establish superiority over approved chemoimmunotherapy. Randomized comparisons must determine whether increased immune stimulation produces a meaningful survival advantage. Source: https://t.co/aLKEXWZ2Vq 🩸 9. Tumors Can Hide Antigens Without Losing Them Researchers at Southern Medical University identified SMPD3, an enzyme involved in sphingolipid metabolism, as an unexpected regulator of tumor antigen presentation. In colorectal cancer models, increasing SMPD3 enhanced MHC-I expression at the cell surface without substantially increasing total MHC-I abundance. The mechanism involved intracellular trafficking rather than greater production of antigen-presenting proteins. SMPD3 overexpression increased CD8 T-cell infiltration, suppressed tumor growth in mice and improved experimental PD-1 blockade responses. This reveals another route to immune escape: cancer cells may retain antigen-presentation machinery but fail to deliver it to their surface. The findings are preclinical. SMPD3 is not yet a validated therapeutic target or clinical biomarker. Source: https://t.co/2J4IGGJiOI 🩸 10. Macrophages May Awaken Sleeping Cancer Cells French researchers uncovered a mechanism through which macrophages can reactivate dormant breast cancer cells. In three-dimensional tumor models, macrophage-derived MMP9 and lysyl oxidase (LOX) remodeled the surrounding extracellular matrix, activating EGFR/HER2 signaling and pushing dormant cancer cells toward renewed proliferation. Remarkably, this signaling occurred without conventional receptor-ligand activation. The finding links macrophage activity, tissue remodeling and metastatic recurrence through a mechanism distinct from classical checkpoint-mediated immune suppression. It raises the possibility that preventing relapse may require controlling the tumor's surrounding tissue environment, not just targeting residual cancer cells. The evidence comes from laboratory models. Its role in human metastatic recurrence and potential for therapeutic intervention remain unproven. Source: https://t.co/Z4TfhFEx9b

Personalized cancer vaccines are becoming a clinical reality! 🧬 INTerpath-001: intismeran + pembrolizumab improves 2-year RFS in resected melanoma: 82.2% vs 70.0% (HR 0.58). A major milestone for mRNA immunotherapy. Now awaiting mature OS data. #ESMO26 @myESMO @OncoAlert https://t.co/VMCCCFpQFy

#ScienceLink #Madrid2026 #ESMO26 #INTerpath001 #Melanoma En INTerpath-001 (fase III; n=1137), añadir intismeran autogene a pembrolizumab adyuvante redujo un 42% el riesgo de recurrencia o muerte frente a placebo + pembrolizumab en melanoma cutáneo IIB–IV completamente resecado. 🧬 Intismeran: terapia de neoantígenos individualizada basada en ARNm. ⏰ Mediana de seguimiento: 24.6 meses ⏳ SLR a 24 meses: 82.2% vs 70.0% HR 0.58 (IC 95%: 0.45–0.75; p<0.001) 📉 SLMD a 24 meses: 88.5% vs 80.2% HR 0.62 (IC 95%: 0.45–0.85; p=0.002) 📊 SG aún inmadura ⚠️ EA grado ≥3 de cualquier causa: 23.6% vs 20.3%. Los EA más frecuentes fueron fiebre, dolor en el sitio de inyección y fatiga. Intismeran continúa en investigación. 🔗Leer/escuchar noticia completa: https://t.co/hkAtpN3iJw

ESMO 2026 | Personalized mRNA Cancer Vaccines Deliver Phase III Success! INTerpath-001: Intismeran + pembrolizumab in resected high-risk melanoma. • RFS: HR 0.58 (42% risk reduction) • 24-month RFS: 82.2% vs 70.0% (+12.2%) • DMFS: HR 0.62 (38% risk reduction) 3 Key Takeaways: 1. Personalized neoantigen vaccines have demonstrated clinically meaningful Phase III efficacy. 2. No major increase in severe treatment-related toxicity, but overall survival data remain immature. 3. Predictive biomarkers, ctDNA/MRD, and optimal sequencing versus neoadjuvant immunotherapy are the next critical questions. A major milestone for personalized oncology. #ESMO26 @myesmo @oncodaily @OncoAlert #CancerVaccines #Melanoma

🧬 Personalized mRNA vaccines work‼️ 📈 INTERPATH-001 met its primary endpoint in resected melanoma patients, paving the way to other tumor types and combinations, including lung 🫁 #cancer 🚀 🌓 One small step for a vaccine, one giant leap for personalized medicine. #ESMO26 @myesmo

First positive trial with individualized neoantigen therapy! Adding intismeran (personalized mRNA vaccine) to pembro improves RFS and DMFS in stage IIB/IIC, III, or IV resected melanoma Opening the door to this approach across different solid tumors! @OncoAlert #Esmo26 https://t.co/lcNNegQ5S0

@DrYukselUrun @weoncologists @myESMO @OncoAlert @OpenMedicineHQ @ProfGLongMIA @FAndreMD @curijoey @DrChoueiri @tompowles1 @CParkMD @PTarantinoMD @VivekSubbiah @montypal @neerajaiims @PGrivasMDPhD @drenriquegrande @marklewismd One Patient. One Tumor. One mRNA Vaccine. 🧬💉
INTErpath-001: Cancer’s custom nightmare just arrived. Ready? 🚀

When urologists are paying attention to Melanoma trials: exciting times for personalized cancer vaccines with the data from INTERPATH-001 excellently presented by @ProfGLongMIA at #ESMO2026! Curious for what’s to come in GU! https://t.co/DvwMBcBTMB

#ESMO26 @myESMO Presidential session presentation by session @ProfGLongMIA INTerpath-001: intismeran + pembro vs pembro in resected stage IIB–IV melanoma (n=1,137) RFS HR 0.58, 2-yr RFS 82% vs 70%
DMFS HR 0.62, 2-yr DMFS 89% vs 80% 1st phase 3 win for an individualized cancer vaccine against an active IO control. OS is pending, but the adjuvant melanoma bar just moved! Moving moment as @ProfGLongMIA paid tribute to Dr. Jeff Weber, who designed this trial and enrolled patients until his passing. Jeff was a dear friend and my colleague at @MoffittNews and today's results are his legacy 💙 Bladder next: INTerpath-005 in MIUC, look forward to seeing the data in future!

I admit i am very much into intismeran…and it seems many others too as it is standing room only here… Fabulous presentation/data on the Interpath-001 trial demonstrating clear benefit of this space age bespoke neoantigen vaccine along w pembro for pts w resected high risk melanoma as to 40% or so improvement in RFS/distant met free survival Indeed a landmark trial for precision medicine and hopefully not too Long before we see confirmation in nsclc/other trials! Interpath- indeed makes us foresee a wonderful path and light ahead for our field! #ESMO26

INTerpath-001 adjuvant Intismeran Autogene + Pembro vs Pembro for resected stage IIB-IV #Melanoma Impressive RFS and distant metastasis free survival improvement with a truly personalized and neoantigen-driven approach @ProfGLongMIA #ESMO26 @myESMO https://t.co/NQ1xb6krW8

@adamfeuerstein @A_May_MD Surgeon's view: they want different things from the operation. Neoadjuvant pembro treats the disease before it comes out. The vaccine is built from the tumour after it's out. INTerpath-001 enrolled patients with no prior systemic therapy, so it doesn't answer the "both" question.

#ESMO26 INTerpath-001 8 Grade 5 AEs in the experimental arm, 0 in the control arm. Of course, it could all be pure coincidence! After all, 6 of the 8 events were not considered TRAE Perhaps it was just the excitement of being randomized to the experimental arm? I'm genuinely curious about the independent causality assessment.

Georgina Long presented INTerpath-001 at #ESMO26: intismeran + pembrolizumab vs placebo + pembrolizumab as adjuvant therapy for resected melanoma. It met the primary RFS endpoint (42% reduction in risk of recurrence or death) and the key secondary DMFS endpoint (38% reduction). OS is still immature, and follow-up is ongoing.

#ESMO26 Starting the Presidential Session with INTerpath-001 Intismeran + pembro shows ⬇️risk of recurrence and of distant mets including high-risk stages. A major step forward for personalised cancer vaccines, looking forward to see the data in other tumour types @OncoAlert https://t.co/SBGq9djNGK

INTerpath-001 - the result of decades of scientific advances and research led to this moment! And brilliant delivery by @ProfGLongMIA Personalized mRNA vaccines + Pembro as adjuvant trt improve RFS for pts with resects IIB-IV Melanoma!! Important points: Tox: a significant number of adverse events occurred BEFORE the vaccine was started Access: the vaccines was given globally #ESMO26 @OncoAlert

#ESMO26 Interpath-01; 🚨addition of individual tumour directed mRNA vaccine intismeran n=1137 patient phIII trial in resected #melanoma to pembro anti-PD1. ⬇️ risk of distant mets or death by 38%. Similar G3-5 TRAEs similar ~14%. OS not mature. 💥A new era in personalised mRNA therapy?

#ESMO26 | LBA1 – INTerpath-001 ✅ First positive Phase 3 of individualized mRNA neoantigen therapy in adjuvant melanoma Intismeran autogene + pembrolizumab vs pembrolizumab alone (Resected stage IIB–IV | N=1,137 | median FU 24.6 mo) ✅ RFS: HR 0.58 (0.45–0.75) | p<0.001 → 24-mo RFS 82.2% vs 70.0% ✅ DMFS: HR 0.62 (0.45–0.85) | p=0.002 → 24-mo DMFS 88.5% vs 80.2% ✅ Benefit across most subgroups ✅ Manageable safety (no potentiation of pembro AEs) ✅ OS still immature New benchmark for adjuvant melanoma. Presented by Georgina V. Long #ESMO26 #Melanoma #mRNA #INTerpath001 @myESMO @OncoAlert

There is clear additive activity with a personalized mRNA vaccine with intismeran autogene with pembrolizumab in melanoma where dual PD1 failed before. Presented by @ProfGLongMIA - I hope the same will come in the future for RCC #ESMO26 #Oncoalert https://t.co/Owe1QY5Uuh

In INTerpath-001, the combination of adjuvant Intismeran plus pembro is superior to pembro alone in resected melanoma mproves RFS in ITT 70% vs 82.2% HR 0.58 #ESMO2026 @darioT_ @myESMO @DrChoueiri @FAndreMD @OncoAlert https://t.co/lKvGZajEEZ

#INTerpath001 amazing adjuvant melanoma trial of a personalized vaccine plus pembrolizumab. 17% of patients didn’t have sufficient tumor sample to create the neoantigen vaccine. DFS highly positive and OS immature. @oncoalert #ESMO26 excited to see other tumor data coming soon! https://t.co/VyUKabIWE2

Phase 3 results from the INTerpath-001 trial confirm that the individualized mRNA vaccine plus pembrolizumab significantly improves outcomes in adjuvant treatment of malignant melanoma. The era of mRNA vaccines in oncology has officially begun!👏 #ESMO26! https://t.co/BO9n6VKQpp

🔥 Presidential Symposium I #ESMO26 INTerpath-001: double-blind phase 3 study of intismeran (mRNA vaccine) + pembro as adjuvant therapy for resected stage IIB–IV #melanoma ✔️ RFS 82.2 vs 70% HR 0.58 ✔️ DMFS 88.5 vs 80.2% HR 0.62 ☣️ No increased risk of toxicity in the combination ✅🧫 mRNA Vaccine in adjuvant melanoma treatment together with anti-PD1 @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @brunolarvol 👇🏽👇🏽

🔥 #ESMO26 INTerpath-001, full data (now yes) On top of RFS HR 0.58 and DMFS HR 0.62: • Manufacturing success >99% • >90% of patients got the maximum 34 neoantigens 🔍 Practice-changing? For a population, yes. Two things still to prove: • Can an mRNA strategy rescue patients primary refractory to neoadjuvant ipi-nivo (no pathologic response)? • Will it move OS in stage II-IIIB too? Resuls in @NEJM soon @myESMO @OncoAlert @Larvol @_SEOM #Melanoma #Immunotherapy

Presidential symposium 1️⃣!! Interpath-001: adjuvant INT (intismeram) plus pembro impact in RFS & DMFS for stage II-IV resectable melanoma #ESMO26 @ProfGLongMIA @myESMO #personalizedmedicine https://t.co/G5Pf70eb1x

A long-awaited breakthrough in cancer vaccines. One patient. One tumor. One personalized mRNA vaccine. INTErpath-001 brings this vision closer to clinical reality. Are we ready to deliver it? @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 @ProfGLongMIA @FAndreMD @curijoey @YJanjigianMD

Welcome INTERpath-001 first mRNA vaccine for melanoma treatment with no potentiation of Pembro AE https://t.co/ZKEYemE2k2

🔥 Personalized cancer vaccines delivering impressive results at #ESMO26! @ProfGLongMIA presents the phase III INTerpath-001 trial in resected high-risk melanoma. Individualized neoantigen mRNA vaccine intismeran autogene + pembrolizumab vs pembrolizumab alone. Key results: 🔹 DMFS: HR 0.62 (95% CI 0.45–0.85), p=0.002 🔹 24-month DMFS: 88.5% vs 80.2% 🔹 RFS: HR 0.58 (95% CI 0.45–0.75) A major milestone for personalized cancer vaccines! A promising step towards truly individualized immunotherapy. #ESMOAmbassador #ESMO26 #Melanoma #CancerVaccines #Immunotherapy

Superb presentation by Georgina Long! INTerpath-001: adding personalized mRNA vaccine intismeran to pembrolizumab reduced recurrence/death risk by 42% in resected stage IIB-IV melanoma (HR 0.58). A major step for cancer vaccines! #ESMO26 @OncoAlert @myESMO #ESMO26 https://t.co/9miRzK7fhb

🔥 full house before #ESMO26 Presidential: 🔹#INTerpath001: Intismeran autogene + pembro vs pembro in resected melanoma 🔹#VOLGA: Periop durva ± treme + EV in MIBC 🔹#DeLLphi-305: Tarlatamab + durva vs durva as 1L maintenance in ES-SCLC 🔹Daro + ADT + RT in very high-risk PCa https://t.co/16kmnFAZaU

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

🔴 Avrupa Onkoloji Kongresi (ESMO 2026)’nde açıklandı! Malign melanomda immünoterapiye, kişiye özel hazırlanmış mRNA kanser aşısının eklenmesi kanserin tekrarlaması veya ölüm riskini %42 azaldı Uzak metastaz riskini de %38 azaldı. Faz 3 INTerpath-001 çalışması. #cancer #oncology #ESMO2026

🆙#ESMO26 Presidential Symposium I 🔥INTerpath-001: Phase 3 Study of the mRNA-Based Individualized Neoantigen Therapy (INT) Intismeran Autogene (Intismeran) Plus Pembrolizumab (Pembro) vs Pembro Alone for Adjuvant Treatment of Resected Stage IIB-IV Melanoma (MEL) 🎙️ @ProfGLongMIA 🔢LBA1 🎯Met Primary Endpoint: Significantly Improved RFS 🎯24-Mo 82.2% vs 70.0%, HR 0.58 🎯DMFS HR 0.62 🎯Grade≥3 AEs 23.6% vs 20.3% ☑️NCT05933577 🔗 https://t.co/Lb6tzuMm0z @OncoAlert @Larvol @myESMO

🌟AND finally, #ESMO26 wouldn't be complete without some of the HEAVY hitters. I expect these data to change practice! 1⃣Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial. I fully expect this trial to establish DLL3 TCE as the dominant first line strategy in SCLC and will likely be practice changing. 2⃣Krascendo 1: Efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. Given the evolution of KRAS G12Ci in this space, what is notable here is the direct prospective comparison to current KRAS G12Ci (adagrasib / sotorasib). Looking forward to ascertain magnitude of potential benefit and safety differences. 3⃣INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL) Technically not a lung cancer study, but I believe this trial to be game-changing from a proof-of-concept approach. In my mind, this study establishes personalized mRNA-based approaches as a viable approach and worthy of research and clinical investment. @lcsmchat @OncoAlert @OncLive @Onco_Nexus @LungCancerEu @Lung_Cancers @LungCancerRx @MedwatchHQ @KRASKickers @SclcSMASHERS @YoungLungCancer

#Madrid #ESMO26 | Main findings from INTerpath-001 released: #Intismeran + #pembrolizumab reduced risk of recurrence or death by 42% (HR, 0.58), risk of distant metastasis or death by 38% (HR, 0.62); 24-monRFS rates 82.2% vs 70.0% | Proud to be part of this effort @MoffittNews

Arriving at #ESMO26 tomorrow just in time for what promises to be one of the most exciting sessions: Presidential Session #1. #INTerpath-001 presented by @ProfGLongMIA, #VOLGA by @tompowles1, #DeLLphi-305 by @sands_jacob & #DASLHiCaP by @niazi_Dr7. A terrific slate of discussants as well, incl @StephenVLiu (one of the most talented orators in our field, IMHO), @MichvdHeijden, @Silke_Gillessen & more. Hats off to @YJanjigianMD, @FAndreMD, @Prof_Nadia_H & #DrJamesLarkin for assembling a powerhouse program! @OncoAlert

💉لقاح mRNA شخصي يقلل خطر عودة سرطان الجلد أو الوفاة بنسبة 42% 📉 أعلنت شركتا Moderna⁠ و Merck⁠ نتائج تجربة INTerpath-001 من المرحلة الثالثة 📉 اختبرت التجربة لقاح Intismeran autogene المصمم خصيصاً وفق الطفرات الجينية لورم كل مريض بشكل شخصي بالإضافة إلى العلاج المناعي Pembrolizumab بعد الاستئصال الجراحي لسرطان الجلد الميلانيني عالي الخطورة 📉 شملت التجربة أكثر من 1,100 مريض 📉 النتيجة 🔹انخفاض الخطر النسبي Relative Hazard Reduction لعودة السرطان أو الوفاة 42% 🔹انخفاض الخطر النسبي للانتشار البعيد أو الوفاة 38% 🔹البقاء دون عودة السرطان مع العلاج المركب 82.2% و تمثل نسبة المرضى الذين بقوا دون عودة السرطان أو الوفاة خلال عامين Recurrence-Free Survival 🔹البقاء دون عودة السرطان مع Pembrolizumab وحده 70% 📉 الأهمية السريرية: يمثل هذا أول دليل من المرحلة الثالثة على فائدة سريرية للقاح سرطاني شخصي قائم على تقنية mRNA عند إضافته إلى العلاج المناعي ❗️النتائج مشجعة انخفاض الخطر النسبي بنسبة 42% لا يعني انخفاض الوفيات وحدها بهذه النسبة بيانات البقاء الكلي غير مكتملة و لم يحصل اللقاح بعد على الموافقات التنظيمية https://t.co/Znw4S3Pl7Z https://t.co/wGMx1VeKui https://t.co/FXD240UPQd

@tonichoueiri with med onc pearls for neoantigen mRNA vaccines. The future is happening now — esp w readout of INTERPATH-001 trial this #ESMO26 @myESMO @oncoalert https://t.co/EhNz2A40yG

I’m in Madrid, and #ESMO26 is underway! Today’s watchlist, Madrid time: opening at 11:30, ESMO-MCBS and KEYNOTE-975 at 13:30, mRNA vaccines at 15:15. INTerpath-001 is tomorrow. Which result will truly change practice? I’ll report from the congress. What are you watching? https://t.co/wzhxRhmqZ9

Encouraging developments in personalised cancer immunotherapy. Phase 3 results from the INTerpath-001 trial suggest that an investigational mRNA-based treatment, intismeran autogene, combined with pembrolizumab, reduced the relative risk of melanoma recurrence or death by 42% compared with pembrolizumab alone. At two years, 82.2% of patients receiving the combination remained free from recurrence, compared with 70% in the control group. The treatment is individually designed using mutations identified in each patient's tumour. Overall survival outcomes remain under evaluation, but these findings represent promising progress towards more personalised approaches to cancer treatment. #Melanoma #CancerResearch #mRNA #Immunotherapy #PrecisionMedicine https://t.co/7gPUjc3Bjh

Topline ESMO data from INTerpath-001 (#Moderna's personalized cancer vaccine) reportedly leaked elsewhere: RFS HR 0.58 (Honestly shame on people for breaking embargo’s). There is a huge divide here between physicians and non-physicians on the outcome. To me, this was huge and clearly worked. This hazard ratio puts it in the company of the most paradigm-changing adjuvant trials in oncology history. Yes, the same outcome can be generated from giving pembro in the neoadjuvant space [SWOG S1801 neoadjuvant + adjuvant pembro vs adjuvant pembro alone: EFS HR 0.58.] That isn't the point. A peptide vaccine strategy yielded the same outcome as having a tumor in vivo. This demonstrates the tech worked, now it can be applied more broadly or potentially even supercharge the neoadjuvant space with less immunogenic tumors. Time to do better and apply to more things (like colon cancer pls). #ESMO26
@OncoAlert @TheGutOncLab

🚨 Scientific embargoes exist for a reason: fair access to data, scientific integrity and, ultimately, patients. Seeing a major #ESMO26 study disclosed ahead of schedule is disappointing. I think ESMO takes its embargo policy seriously, and I would expect a breach of this magnitude to have consequences. Science should set the timeline, not the stock market 😡 With INTerpath-001, someone clearly took a shortcut on the path to the data. @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma

Cautionary note – personalized mRNA neoantigen vaccine (intismeran / mRNA-4157) in resected melanoma. The reported reduction in recurrence is real, yet several core uncertainties remain unresolved. The control was an inactive placebo, not a scrambled or irrelevant mRNA matched for mass and antigen number. Non-specific innate effects of the mRNA-LNP platform therefore cannot be separated from antigen-specific activity. No published in vitro data have tested whether the encoded neoantigen peptides or mRNA constructs exert any direct stimulatory or pro-proliferative effect on melanoma cells independent of the immune system. This possibility has not been experimentally excluded. Overall survival benefit is still immature, and the contribution of the vaccine outside the adjuvant Keytruda combination is unproven. Manufacturing time, cost, and scalability constraints are substantial; generalizability beyond highly selected resected melanoma remains limited. These open questions do not erase the clinical signal. They do limit how confidently the mechanism and the true incremental value of the personalized neoantigens can be asserted.

ツチノコ的ESMOレビュー① いきなり情報解禁前にデータが漏れるという大波乱の幕開けです。 モデルナの株価が25%下落の 大・暴・落！！ 個別化mRNAがんワクチン 「intismeran autogene」 の第Ⅲ相試験、INTerpath-001ですね。 すでにデータが世に出てしまったため、ESMOが正式に情報解禁を前倒ししました。 これ、何をやっているかというと、、 患者さんのがんの遺伝子情報を調べて、その人のがんに特有の目印を狙うmRNAワクチンを作る。 それを使って、免疫に 「この目印のあるがん細胞を攻撃してくれ」 と教える治療です。 患者さんごとに作る、オーダーメイドのがんワクチンですね。 今回の対象は完全切除後のStage IIB〜IVの悪性黒色腫の患者さん1,137人。 ①個別化mRNAがんワクチン＋キイトルーダ（Pembrolizumab） ②キイトルーダ単独 を比較しています。 結果は、、 【2年無再発生存率】 82.2％ vs 70.0％ HR 0.58、p＜0.001 再発または死亡のリスクが42％低下。 【2年遠隔転移無生存率】 88.5％ vs 80.2％ HR 0.62、p＝0.002 遠隔転移または死亡のリスクが38％低下。 Grade 3〜5の治療関連有害事象は 14.2％ vs 13.4％でした。 全生存期間はまだ追跡が必要ですが、キイトルーダに上乗せして再発を減らしたというのは、臨床的には重要な結果だと思います。 ところが、、 モデルナの株価は、データ公開後に25％超下落したと報じられています。 「え、効いてるのに何で？」 ってなりますよね。 そもそもモデルナ株は、今回の治療への期待などから年初来500％超も上昇していました。 なので、良い結果が出ること自体は、すでに株価に織り込まれていたという話です。 加えて、先行する第Ⅱ相試験から期待されていたほどには 遠隔転移を抑える効果が大きくなかった、という受け止めもあったようです。 ただし、対象や追跡期間の違う試験をそのまま比較して「効果が落ちた」とは言えません。 個人的には、患者さんごとに作るmRNAがんワクチンが、第Ⅲ相で再発抑制効果を示したこと自体が大きいと思います。 ただ、これで色々ながんに効くと決まったわけではありません。 まずはメラノーマでの結果として評価して、OSと他のがん種の試験の結果を今後は見ていきたいですね。 ツチノコ的には数十年もすればゲノム含めがん治療は完全に個別化される可能性があると思っているので 標準治療の教育体系から変えていかなくてはならないのでは？ という印象です。 公式資料： https://t.co/NWcEXu7k0B⁠ #ESMO26 米モデルナの株価が一時26%安　治験データ漏洩、期待に届かず：日本経済新聞 https://t.co/ZM4mZ3zM9N

✈️ En route to Madrid for #ESMO26, landing just in time for the data to start Friday morning. Most excited for: VOLGA LBA2 in bladder cancer, INTerpath-001's first phase 3 neoantigen win, LITESPARK-011 final in kidney cancer, and DASL-HiCaP in prostate. What a week ahead 🔬 #GUonc

@adamfeuerstein Fair point on the control arm: for macroscopic stage III, neoadjuvant IO is now the bar (NADINA/S1801). But resected IIB/C and microscopic stage III have no neoadjuvant option — that's where INTerpath-001 matters. OS and subgroups will decide. #ESMO26

‼️ Interesting commentary on INTerpath-001 No need for vaccine if pembro given neoadjuvant? Wow, await further details / data here, but what a dud! Precision/Personalized dud https://t.co/i1SNiVUjfz

The vaccine, intismeran autogene, is built from each patient's own tumor and encodes up to 34 of its mutations. In the earlier Phase 2b melanoma trial, adding it to Keytruda cut the risk of recurrence or death by 49% at five years. https://t.co/tjBUoTvtoJ

@amedinacol No. Neoadjvant treatment was not allowed in Interpath-001. So, it compares to adjuvant (definitely not peri-operative) pembro. I’d argue the NIVIDA regime is a better deal than Interpath-001 for most of the patients.

🚨 ESMO 2026 | INTErpath-001 (LBA1) - as data is released by Esmo 🔹 24-month RFS: 82.2% vs 70.0% HR 0.58 (95% CI 0.45–0.75); P<0.001 🔹 24-month DMFS: 88.5% vs 80.2% HR 0.62 (95% CI 0.45–0.85); P=0.002 🔹 Grade ≥3 adverse events: 23.6% vs 20.3% The trial randomized 1,137 patients with resected stage IIB–IV melanoma. Both arms received pembrolizumab; the experimental arm added an individualized mRNA neoantigen therapy. The key question now: will better recurrence control translate into an overall survival benefit? Looking forward to full dataset on day 2 . #ESMO26 @myESMO

Looking forward to the presentation and discussion. #LBA1 Phase 3 INTerpath-001 trial results at #ESMO26 👉🏽The Kaplan-Meir curves don’t always tell the whole story. Side effects, cost, access matter but 👉🏽Its is very exciting that a personalized mRNA technology can be used to control cancer recurrence.

@OncoAlert @brunolarvol @adamfeuerstein An alleged third-party leak of the top plenary presentation of the #interpath-001 at #ESMO2026 . Source still unknown. #Intismeran autogene + pembro reportedly reduced recurrence or death (EFS) risk by 42% (HR 0.58) for resected IIB-IV #melanoma Possible #PracticeChanging pending safety and full text publication

Topline ESMO data from INTerpath-001 (#Moderna’s personalized cancer vaccine) reportedly leaked elsewhere: DFS HR 0.58 This hazard ratio puts it in the company of the most paradigm-changing adjuvant trials in oncology history: https://t.co/MPruTftgJO

Promising results from DeLLphi-305 at #ESMO26! Tarlatamab + durvalumab maintenance improved median OS from 12.7 to 21.1 months in extensive-stage SCLC. An exciting step forward in a disease with limited therapeutic options! #LungCancer https://t.co/ZpNzMvQL6p

In a prespecified interim analysis of a phase 3 trial involving patients with extensive-stage SCLC, the median overall survival was 21.1 months with #Tarlatamab maintenance therapy and 12.7 months with durvalumab alone. #ESMO26 https://t.co/xuqEkJZSSn https://t.co/FBAHoeWXyv

#ESMO26 PS I wrap-up, 4 LBAs, all positive: • INTerpath-001 RFS HR 0.58 • VOLGA EFS HR 0.51 • DeLLphi-305 OS HR 0.42 (21.1 vs 12.7 mo) • DASL-HiCaP MFS HR 0.42 Safety definitions differ. Which one made you think most? https://t.co/294mwvfK2H

Lots of exciting developments at #ESMO26! Several important studies were also published simultaneously in major medical journals. A few highlights: 1. Small-cell lung cancer (NEJM): Adding tarlatamab to first-line durvalumab maintenance improved median overall survival from 12.7 to 21.1 months in the phase 3 DeLLphi-305 trial. 2. HER2-positive breast cancer (NEJM): Anbenitamab, a HER2-targeted bispecific antibody, plus HB1801 improved 24-month progression-free survival to 58.5% vs 34.4% with standard therapy (HR 0.46). 3. Muscle-invasive bladder cancer (NEJM): Perioperative durvalumab plus neoadjuvant enfortumab vedotin improved 24-month event-free survival to 63.5% vs 45.1% with surgery alone. 4. HR-positive, HER2-negative breast cancer (Lancet): The EGFR/HER3-targeted bispecific antibody-drug conjugate izalontamab brengitecan doubled median progression-free survival versus chemotherapy (8.2 vs 4.0 months; HR 0.41) in the phase 3 PANKU-Breast01 trial. 5. Melanoma (Nature Medicine): Five-year RELATIVITY-047 results showed sustained overall survival benefit with nivolumab + relatlimab vs nivolumab alone (HR 0.78). Full publications below 👇

🦉 Cancer Immunotherapy: A Week of Breakthroughs, Setbacks and New Biological Insights October 17–24, 2026 This week brought two major clinical advances: a personalized mRNA cancer vaccine significantly reduced melanoma recurrence, while a T-cell engager sharply extended survival in aggressive lung cancer. Other studies revealed why CAR-T cell quality, antigen presentation, and the tumor microenvironment can matter as much as immune activation itself. 🩸 1. A Personalized Cancer Vaccine Passes Its Biggest Test Moderna and Merck's individualized mRNA vaccine, intismeran autogene, reduced melanoma recurrence or death by 42% when combined with pembrolizumab in the Phase 3 INTerpath-001 trial. Among 1,137 patients with resected stage IIB–IV melanoma, two-year recurrence-free survival reached 82.2% versus 70.0% with pembrolizumab alone. Distant metastasis or death risk fell 38%, without a substantial increase in severe treatment-related toxicity. The results provide major randomized evidence that vaccines targeting patient-specific tumor mutations can improve clinical outcomes, not merely generate immune responses. Overall-survival data remain immature, and personalized manufacturing presents practical challenges. Source: https://t.co/FHlL1f9wPs 🩸 2. T-Cell Engagers Nearly Double Survival in Lung Cancer The Phase 3 DeLLphi-305 trial showed that adding Amgen's DLL3-targeted T-cell engager tarlatamab to durvalumab maintenance therapy extended median survival from 12.7 to 21.1 months in extensive-stage small-cell lung cancer. Among 563 patients, the combination reduced mortality risk by 58% and increased progression-free survival from 1.9 to 7.4 months. Tarlatamab recruits T cells directly to cancer cells, complementing durvalumab's PD-L1 blockade. The survival advantage is substantial, but cytokine-release syndrome occurred in 49.6% of patients, predominantly grade 1–2. Grade ≥3 treatment-related adverse events affected 20.9% versus 10.8%. These results could reshape first-line maintenance treatment, subject to regulatory review. Source: https://t.co/1TRq9VtseZ 🩸 3. Bladder Cancer Treatment Takes a Major Step Forward The Phase 3 VOLGA trial demonstrated a significant survival advantage with enfortumab vedotin plus durvalumab in patients with muscle-invasive bladder cancer unable or unwilling to receive cisplatin. Among 462 patients, the combination reduced the risk of progression, recurrence or death-related events by 49%. Two-year event-free survival reached 64% versus 45%, while overall survival was 78% versus 69%. The strategy combines targeted cytotoxic delivery through an antibody–drug conjugate with PD-L1 checkpoint inhibition. However, grade 3–4 adverse events occurred in 64% versus 44%. The results support a new perioperative option, although comparisons with other modern regimens remain unavailable. Source: https://t.co/VLXeYEzs9O 🩸 4. CAR-T Quality May Matter More Than Expansion A multicenter study involving 783 lymphoma patients found that CAR-T products enriched in naïve-like CCR7⁺CD45RA⁺ T cells were associated with significantly longer progression-free survival. In the primary cohort of 580 patients receiving axi-cel, these cells predicted better outcomes (HR 0.46; p=9.8×10⁻⁵), independently of tumor burden, inflammation and CAR-T expansion. An additional 203 patients confirmed the association. More previous treatment lines were linked to fewer naïve-like cells. The implication challenges a familiar assumption: expanding more CAR-T cells may be less important than preserving cells capable of sustained antitumor activity. Whether manufacturing changes that enrich these populations actually improve survival remains unproven. Source: https://t.co/GAN67wP3OV 🩸 5. A New Approach to Severe Immunotherapy Toxicity Researchers in Germany and Switzerland reported promising results using extracorporeal photopheresis to treat severe immune-related complications resistant to corticosteroids. The technique treats collected immune cells with a photosensitizing agent and ultraviolet light before returning them to circulation. In a prospective Phase 1b/2 study involving 30 patients, the response rate among evaluable inflammatory complications reached 96.3%, including responses in colitis, hepatitis and dermatitis. Treatment reduced inflammatory T-cell activity, including granzyme expression and interferon-γ/TNF signaling. No treatment-related serious adverse events occurred. The potential advantage is controlling dangerous inflammation without escalating systemic immunosuppression. However, the uncontrolled study cannot establish comparative efficacy or confirm preservation of antitumor immunity. Source: https://t.co/xDE6iBNXhy 🩸 6. Selective T-Cell Activation Shows Activity in Resistant Tumors Invikafusp alfa, an experimental bispecific antibody, activates selected T-cell populations expressing Vβ6 or Vβ10 T-cell receptors rather than broadly stimulating the immune system. In the Phase 1/2 START-001 trial, 4 of 27 patients (14.8%) treated at biologically optimal doses achieved objective responses, while 59.3% experienced disease control. Responses included microsatellite-stable colorectal cancer and PD-L1-negative lung cancer, where conventional checkpoint inhibition often has limited efficacy. The treatment expanded memory-like target T cells without broadly activating unrelated populations. This demonstrates preliminary clinical activity, not established benefit. Patient numbers remain small, durability is uncertain, and cytokine-release syndrome remains a risk. Source: https://t.co/2KupIGrKnT 🩸 7. Strong Vaccine Immunity Fails to Improve Pancreatic Cancer Outcomes The randomized Phase 2 AMPLIFY-7P trial tested camupepimut (ELI-002 7P), an off-the-shelf vaccine targeting mutant KRAS, in 144 patients with pancreatic cancer after standard treatment. Despite vaccine-specific T-cell responses in 98.9% of evaluable patients, the primary disease-free survival endpoint was missed: 23.8 versus 21.2 months (HR 0.85; p=0.5329). Subgroup analyses suggested possible benefit in patients without detectable circulating tumor DNA (HR 0.51) or prior radiotherapy (HR 0.59). The contrast is striking: nearly universal immune activation did not translate into a significant overall clinical benefit. Vaccination may work better against minimal residual disease, but subgroup signals remain exploratory and clinical efficacy is unproven. Source: https://t.co/18SHt23Nqc 🩸 8. Dual Checkpoint Blockade Targets Difficult Biliary Cancers Chinese investigators reported Phase 2 results for cadonilimab, a bispecific antibody blocking PD-1 and CTLA-4, combined with gemcitabine and cisplatin in advanced biliary tract cancer. Among 61 patients, the objective response rate reached 55.7%, with disease control in 85.2%. Median progression-free survival was 8.0 months and overall survival 15.6 months. Dual checkpoint blockade could provide broader immune activation than PD-1/PD-L1 inhibition alone. However, grade ≥3 adverse events occurred in 68.9%, including severe immune-related events in 18%. The single-arm design cannot establish superiority over approved chemoimmunotherapy. Randomized comparisons must determine whether increased immune stimulation produces a meaningful survival advantage. Source: https://t.co/aLKEXWZ2Vq 🩸 9. Tumors Can Hide Antigens Without Losing Them Researchers at Southern Medical University identified SMPD3, an enzyme involved in sphingolipid metabolism, as an unexpected regulator of tumor antigen presentation. In colorectal cancer models, increasing SMPD3 enhanced MHC-I expression at the cell surface without substantially increasing total MHC-I abundance. The mechanism involved intracellular trafficking rather than greater production of antigen-presenting proteins. SMPD3 overexpression increased CD8 T-cell infiltration, suppressed tumor growth in mice and improved experimental PD-1 blockade responses. This reveals another route to immune escape: cancer cells may retain antigen-presentation machinery but fail to deliver it to their surface. The findings are preclinical. SMPD3 is not yet a validated therapeutic target or clinical biomarker. Source: https://t.co/2J4IGGJiOI 🩸 10. Macrophages May Awaken Sleeping Cancer Cells French researchers uncovered a mechanism through which macrophages can reactivate dormant breast cancer cells. In three-dimensional tumor models, macrophage-derived MMP9 and lysyl oxidase (LOX) remodeled the surrounding extracellular matrix, activating EGFR/HER2 signaling and pushing dormant cancer cells toward renewed proliferation. Remarkably, this signaling occurred without conventional receptor-ligand activation. The finding links macrophage activity, tissue remodeling and metastatic recurrence through a mechanism distinct from classical checkpoint-mediated immune suppression. It raises the possibility that preventing relapse may require controlling the tumor's surrounding tissue environment, not just targeting residual cancer cells. The evidence comes from laboratory models. Its role in human metastatic recurrence and potential for therapeutic intervention remain unproven. Source: https://t.co/Z4TfhFEx9b

Amazing result from Delphi 305 study in SCLC presented at ESMO! Tarlatamab plus Durvalumab as maintenance in 1.line treatment most likely new standard. However, better than Tarlatamab in 2.line, which is current SOC? https://t.co/61P4GpLYgx

🚨 PRACTICE-CHANGING in #SCLC! DeLLphi-305: tarlatamab + durvalumab maintenance ✅ 58% ↓ risk of death ✅ Median OS 21.1 vs 12.7 months ✅ 66% ↓ progression/death A huge advance for historically underserved patients with poor outcomes. 🇬🇧 Let’s expedite UK approval & NHS access

NEJM: in spread small-cell lung cancer, adding tarlatamab to durvalumab after first treatment: typical survival 21.1 vs 12.7 months (563 people). Caveat: early look, maker-funded. https://t.co/dNrKCTysk0 Buy ScienceTees here: https://t.co/OJvtjxB5Wu https://t.co/x5aGAUD3wA

The moment I saw the overall survival curves, I wanted to stand up and applaud! 👏 40,000 of us at #ESMO26, sharing the same excitement and hope not for ourselves, but for our patients. ❤️ A truly emotional moment in #SCLC. #DeLLphi305 @StephenVLiu @sands_jacob @lungoncdoc https://t.co/FxDFvv1EMP

Outstanding discussion by @StephenVLiu on the practice-changing DeLLphi-305 trial @sands_jacob . A new chapter in the treatment of ES-SCLC! #ESMO26. One year ago, we anticipated that we might finally be bending gravity. Today, that vision is becoming a reality!!!!!!👏👏👏👏👏 https://t.co/QDMrTH5l8L

#ESMO26 #DeLLphi305 Tarlatamab in Combination With Durvalumab vs Durvalumab Alone in Subjects With Extensive-Stage Small-Cell Lung Cancer Following Platinum, Etoposide and Durvalumab Are we changing prognosis of SCLC? Yes we are. Results speak for themselves. OS 21.1m vs 12.7 m

DeLLphi-305 a new standard of care in ES-SCLC Tarlatamab maintenance + Durvalumab after induction chemo-IO Huge win against SCLC! Congrats @sands_jacob and DeLLphi-305 group And a standing ovation! 👏🏼 https://t.co/a4380aJDuB

I very much enjoyed the discussion by @StephenVLiu of DeLLphi-305 (tarlatamab + durvalumab as maintenance therapy in ES-SCLC at #ESMO26 👏👏👏 #ESMOAmbassadors https://t.co/Wl31gpUtEu

@sands_jacob with Dellphi305 — tarlatamab w durvalumab vs durvalumab for small cell lung cancer — almost doubling of overall survival w manageable CRS & outpatient treatment. Standing ovation for small cell! @nejm concurrent pub today. @oncoalert @myESMO #ESMO26 https://t.co/Z25EA6hQL2

Standing ovation at #ESMO26! 👏 Practice-changing Phase 3 results from DeLLphi-305 (LBA3) for maintenance tarlatamab + durvalumab in 1L ES-SCLC: mOS: 21.1 vs 12.7 mo (HR 0.42; p < 0.001) A new standard of care with BiTE + ICI💥 https://t.co/2TAEwtvbnY

Striking results from DeLLphi-305 in SCLC topped with an emotional standing ovation. Mainteinance Tarlatamab is actually more like a second induction-treatment rather than a proper mainteinance! Kudos to @sands_jacob for the magistral presentation #ESMO26 #ESMOAmbassadors https://t.co/2w1PXt8jLu

DeLLphi-305 at #ESMO26, presented by Jacob Sands, got a standing ovation. An important advance in very aggressive biology. Tarlatamab + durvalumab vs durvalumab as 1L maintenance in ES-SCLC: ▪️ OS HR 0.42, median 21.1 vs 12.7 mo ▪️ PFS HR 0.34 ▪️ ORR 26.4% vs 4.1% Important to study in NEPC and small cell bladder.

Expert discussion of DeLLphi-305 by @StephenVLiu. Bringing tarlatamab to maintenance is major advance as second line tarlatamab is often “a promise we cannot keep.” Many patients never receive 2nd line. #ESMO26 https://t.co/T6IRxIS8ev

🚨 Impressive results from #ESMO2026! Phase III DeLLphi-305: Tarlatamab + durvalumab vs durvalumab alone as 1L maintenance in ES-SCLC: 🔹 Median OS: 21.1 vs 12.7 months (HR 0.42) 🔹 Median PFS: 7.4 vs 1.9 months (HR 0.34) 🔹 ORR: 26.4% vs 4.1% 🔥 Practice-changing potential! #LungCancer #SCLC @OncoAlert @weoncologists @StephenVLiu @GlopesMd @ManuelDomine

In DeLLphi-305: The combination of Tarlatamab+ Durvalumab improves both OS (21 vs 12 months HR 0.42) and PFS in ES-SCLC. This is remarkable in such a lethal disease with high recurrence rates and mortality. #ESMO2026 #ESMOAmbassadors @myESMO @StephenVLiu @tompowles1 @FAndreMD https://t.co/fE2K7k2Jha

🔥 Hot off the press! 📄! Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer | New England Journal of Medicine https://t.co/mgUWrdUWme

Standing ovation at #ESMO2026 for DELLPHI-305. It is heart-warming to see a meaningful survival advantage in ED-SCLC. https://t.co/ZkEwRPh2v6

Starlatamab takes a huge BiTE today out of small cell lung cancer! Amazing PFS (0.34) and OS (0.42) HR and truly manageable added tox- 50% CRS but almost uniformly gr 1/2 and near non-existent ICANS, no new safety signal w durva combo just makes this one of the most impressive SCLC trials/ cancer trials ever.. Given extreme need for better treatments for our pts w ES-SCLC, unprecedented benefit seen in DeLLphi-305 plus availability/experience with use already it is a no-brainer to incorporate into our practice as SOC maintenance therapy on Monday… well, not Mon- whenever your flight takes you back post-#ESMO26 Amazing job by @sands_jacob and Amgen/DeLLphi team- glad we had a chance to offer such a transformational trial to our pts as well at Monte/Einstein! With these extraordinary results starlatamab is likely to continue to expand into 1st line/LS-SCLC settings and lets just dream on- if we as a field have taken such a tasty first BiTE, can hardly wait for the next one! Standing ovation- well deserved! #lcsm

#ESMO26 | DeLLphi-305 Maintenance tarlatamab + durvalumab prolonged median OS to 21.1 vs 12.7 months with durvalumab alone in ES-SCLC at the prespecified interim analys @NEJM @myESMO @Larvol https://t.co/5YjJCDcyNi

🚨 ESMO 2026 | DeLLphi-305 Tarlatamab + durvalumab delivers impressive survival benefits in 1L maintenance ES-SCLC! ✅ OS: 21.1 vs 12.7 mo (HR 0.42) ✅ PFS: 7.4 vs 1.9 mo (HR 0.34) Benefits maintained across key subgroups, including brain and liver metastases. 🔥 New SOC 💫💫 https://t.co/bEhzHFst9o

🔥 Presidential Symposium I #ESMO26 🗣️ @sands_jacob @DanaFarber DeLLphi-305 trial evaluating tarlatamab + durva vs durva as 1LM therapy for ES-SCLC. ✔️ mOS 21.1 vs 12.7m HR 0.42 ✔️ mPFS 7.4 vs 1.9m HR 0.34 ✔️ ORR 26.4 vs 4.1% ☣️ 46.8 vs 40.6% grade 3 or higher @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @NEJM @brunolarvol 👇🏽👇🏽

🔥🔥🔥 #ESMO26 DeLLphi-305 in @NEJM Tarlatamab + durva vs durva as 1L maintenance in ES-SCLC (n=563) ➡️ mOS 21.1 vs 12.7 mo | HR 0.42 ➡️ mPFS 7.4 vs 1.9 mo | HR 0.34 ➡️ ORR 26% vs 4% | CR 0.9% | mDoR 12.7 mo ➡️ G≥3 AEs 47% vs 41% | CRS in ~50%, mostly G1-2, manageable 🔍 OS here is a game changer. New 1L maintenance standard, ahead of lurbi-atezo. 🙋CRs almost absent and DoR ~1 year. Still far from the long-term tail we see with PD-1 blockade in other tumour types. We can’t cure without CRs @myESMO @_SEOM @OncoAlert @Larvol #LCSM #SCLC

Presidential symposium 1️⃣!! DeLLphi-305 study: Tarlatamab + durva significantly improved ✅ OS, PFS, and ORR ‼️ in 1LM ES-SCLC @myESMO #ESMO26 a 🆕 standard of care! https://t.co/TJw3Q74PNE

DeLLphi-305; ES-SCLC; nearly 2y mOS; Strong PFS signal; this is about the strongest data I’ve seen in this space. @BTOGORG #ESMO26 https://t.co/rukehL59lQ

📖 A new chapter in SCLC therapy has been written by @sands_jacob 💥 DeLLphi-305 sets a new standard of care in maintenance after induction chemo-io for patients with ES-SCLC #ESMO26 @myESMO https://t.co/vVhg7SmgsL

DeLLphi-305 @NEJM #ESMO26 ➡️Pts with ES-SCLC without progression after initial chemo-IO randomized to tarlatamab–durvalumab with durvalumab as 1L maintenance therapy ➡️ Md OS 21.1 mo (tarla arm) vs 12.7 months ➡️Md PFS 7.4 mo (tarla arm) vs 1.9 mo Practice changing and now a new standard of care #LCSM @OncoAlert https://t.co/BM6jNTyFw6

Real-time first-line updates in ES-SCLC! Getting closer and closer to a 2yr mOS. Tarlatamab + Durvalumab maintenance improved mOS to 21.1 months compared to 12.7 months with single agent Durva. New standard of care in this space! https://t.co/9kDH9ap8HL

#ESMO26 Presidential 1 : #SCLC DeLLphi-305: Who would have imagined some years ago that median OS of SCLC would equal that of non-AGA NSCLC! #Tarlatamab as 1L maintenance with Durvalumab after induction chemoIO in ES-SCLC improved OS from 12.7 to an impressive 21.1m, corresponding to a HR of 0.42. 80% of patients alive and 38% progression-free at 12 months The dawn of a new era for thoracic oncology and for the lives of our patients 💫✨ @myESMO @SclcSMASHERS #ESMOAmbassadors

@Reuters In the DeLLphi-305 results, median overall survival was 21.1 months with tarlatamab plus durvalumab maintenance versus 12.7 months with durvalumab alone.

From #ESMO26 & @NEJM Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer https://t.co/locTy831XT Practice changing data for a terrible disease with hazard ratios that are unequivocal.

🚨🔥@OncoAlert Hot off the press. Just published @NEJM in conjunction with presentation @myESMO #ESMO26 the long-awaited #PracticeChanging results of: ⭐️#DeLLphi305 phase 3 trial of: ❇️1st line maintenance #Tarlatamab + #Durvalumab) vs #Durvalumab alone in patients with #ExtensiveStage #SmallCell #LungCancer after initial induction Tx with #Chemo + Durvalumab. Study showed: ‼️#Impressive statistically significant & clinically meaningful ⬆️#OverallSurvival Benefit. ✅#mOS: 21.1 vs 12.7 months (HR 0.42) ✅12-month OS: 79.4% vs 53.3% ✅#mPFS: 7.4 vs 1.9 months (HR 0.34) ⚠️ Grade ≥3 #AEs: 46.8% vs 40.6% * In Tarlatamab arm: #CRS: 49.6% (Grade ≥3: 0.4%) #ICANS: 1.1% (Grade ≥3: 0%) 👇🏻 https://t.co/JoYBDSUAo9

🔥 full house before #ESMO26 Presidential: 🔹#INTerpath001: Intismeran autogene + pembro vs pembro in resected melanoma 🔹#VOLGA: Periop durva ± treme + EV in MIBC 🔹#DeLLphi-305: Tarlatamab + durva vs durva as 1L maintenance in ES-SCLC 🔹Daro + ADT + RT in very high-risk PCa https://t.co/16kmnFAZaU

WOW! BIG news for our patients with extensive-stage small cell lung cancer! Phase 3 DeLLphi-305 trial, adding tarlatamab to durvalumab maintenance after initial chemoIO: ✅ OS: 21.1 vs 12.7 months (HR 0.42) ✅ PFS: 7.4 vs 1.9 months (HR 0.34) Practice-changed! #ESMO26 https://t.co/t23SBNzfUD

🔥🔥#ESMO26 Top Thoracic Abstracts: #DeLLphi305: Phase III (n=563): Tarlatamab + Durvalumab vs Durvalumab as 1L maintenance after chemo-IO in ES-SCLC Definitely practice changing if we are able to deliver to more pts in the community , moving tarlatamab 1L maintenance ▶️Median OS: 21.1 vs 12.7 months (HR 0.42) 🔥 ▶️12-month OS: 79.4% vs 53.3% ▶️Median PFS: 7.4 vs 1.9 months (HR 0.34) ▶️ORR: 26.4% vs 4.1% ⚠️ Grade ≥3 AEs: 46.8% vs 40.6%; CRS 49.6% (mostly low grade). #lcsm @SclcSMASHERS

🔥 TODAY COULD BE ONE OF THE DEFINING MOMENTS OF #ESMO26! 🔥 The ESMO Presidential Symposium is always one of the highlights of the congress, and today’s session promises some truly extraordinary science! If I had to pick ONE study with the greatest potential to change clinical practice at ESMO 2026, my choice would be DeLLphi-305. For decades, SCLC has been one of the most challenging diseases in oncology, with far too little progress and far too few therapeutic breakthroughs. Could DeLLphi-305 finally represent the major leap forward we have been waiting for? We already know that adding tarlatamab to durvalumab as first-line maintenance significantly improves OS compared with durvalumab alone. But today, we will finally see the numbers. And I am genuinely excited to discover just how transformative this benefit might be! My personal bet for the biggest breakthrough of #ESMO26? DeLLphi-305. @StephenVLiu @sands_jacob Of course, the magnitude of survival benefit, safety and clinical applicability will ultimately determine its impact. But the potential is enormous. Don’t miss today’s Presidential Symposium! Madrid | 🕟 16:30 CEST Alicante auditorium #ESMO26 #ESMOAmbassador #SCLC #LungCancer #Immunotherapy #Oncology #PracticeChanging

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

JUST IN: DeLLphi-305: Small Cell Lung Cancer Extensive-Stage Phase III (n=563): Tarlatamab + Durvalumab vs Durvalumab as 1L maintenance after chemo-IO, to be presented by our own @sands_jacob from @DanaFarber • Median OS: 21.1 vs 12.7 months (HR 0.42) • Median PFS: 7.4 vs 1.9 months (HR 0.34) • ORR: 26.4% vs 4.1% Grade ≥3 AEs: 46.8% vs 40.6%; CRS 49.6% (most low grade). Probably new standard of care in ES-SCLC. @OncoAlert @DanaFarberNews #ESMO26

🆙#ESMO26 Presidential Symposium I: #LCSM 🔥DeLLphi-305: Tarlatamab Plus Durvalumab (Durva) vs Durva as 1L Maintenance (1LM) Therapy Following Durva, Platinum, and Etoposide in Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Primary Analysis of the Phase 3 Trial 🎙️ @sands_jacob 🔢LBA3 🎯Met Primary Endpoint: Significantly Improved OS 🎯mOS 21.1 vs 12.7m, HR 0.42 🎯mPFS 7.4 vs 1.9m, HR 0.34 🎯ORR 26.4% vs 4.1% 🎯CRS 49.6% (Mostly Low Grade), No Fatal Events ☑️NCT06211036 🔗 https://t.co/Lb6tzuMm0z @OncoAlert @Larvol @myESMO @IASLC

DeLLphi-305 - tarlatamab added to durvalumab after initial chemo-immunotherapy for small lung cancer essentially doubles survival. Hope for all cancers here, if the right target & treatment modality can be refined. Unquestionably a new standard for this disease. #ESMO2026 https://t.co/8ovQ2yB6fr

#ESMO26 DeLLphi-305: tarlatamab+durva vs durva, 1L maintenance ES-SCLC ➡️ OS 21.1 vs 12.7 mo, HR 0.42 ➡️ PFS 7.4 vs 1.9 mo, HR 0.34 ➡️ CRS 49.6% (G3+ 0.4%) Amazing to be part of this practice-changing study on the global steering committee!! @LungCancerRx @OncoAlert @oncodaily https://t.co/BfjokrDpim

🌟AND finally, #ESMO26 wouldn't be complete without some of the HEAVY hitters. I expect these data to change practice! 1⃣Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial. I fully expect this trial to establish DLL3 TCE as the dominant first line strategy in SCLC and will likely be practice changing. 2⃣Krascendo 1: Efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. Given the evolution of KRAS G12Ci in this space, what is notable here is the direct prospective comparison to current KRAS G12Ci (adagrasib / sotorasib). Looking forward to ascertain magnitude of potential benefit and safety differences. 3⃣INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL) Technically not a lung cancer study, but I believe this trial to be game-changing from a proof-of-concept approach. In my mind, this study establishes personalized mRNA-based approaches as a viable approach and worthy of research and clinical investment. @lcsmchat @OncoAlert @OncLive @Onco_Nexus @LungCancerEu @Lung_Cancers @LungCancerRx @MedwatchHQ @KRASKickers @SclcSMASHERS @YoungLungCancer

DeLLphi-305 (LBA3): tarlatamab + durva vs durva maintenance in ES-SCLC without progression after durva + platinum-etoposide. OS HR 0.42 (CI 0.32-0.54); 12-mo OS 79% vs 53%, median OS 21 vs 13 mo. Impressive OS signal. Was thoracic consolidation RT allowed? The abstract doesn't say. If so, would be interested to see fractionation/dosing schemes and how RT was interdigitated. #ESMO26 #radonc https://t.co/wazLJ6ejpv

🚨 ESMO 2026 presidential | DeLLphi-305: Phase III (n=563): Tarlatamab + Durvalumab vs Durvalumab as 1L maintenance after chemo-IO. 📊 Key results: • Median OS: 21.1 vs 12.7 months (HR 0.42) 🔥 • 12-month OS: 79.4% vs 53.3% • Median PFS: 7.4 vs 1.9 months (HR 0.34) • ORR: 26.4% vs 4.1% ⚠️ Grade ≥3 AEs: 46.8% vs 40.6%; CRS 49.6% (mostly low grade). 💡 58% reduction in risk of death! Could this redefine first-line maintenance in ES-SCLC? Probably yes. Looking forward towards full data set . @OncoAlert @esmo #esmo26 #SCLC #DeLLphi305

#ESMO26 | DeLLphi-305 – Phase III | Presidential Symposium-1 In ES-SCLC, tarlatamab + durvalumab maintenance significantly improved outcomes vs durvalumab alone following first-line chemotherapy + durvalumab: OS: 21.1 vs 12.7 months (HR 0.42) PFS: 7.4 vs 1.9 months (HR 0.34) CRS: 49.6%; grade ≥3: 0.4%. An impressive OS benefit! Atezolizumab + lurbinectedin maintenance also demonstrated an OS benefit in IMforte (HR 0.73). Although cross-trial comparisons are inappropriate, the magnitude of the OS benefit with tarlatamab appears numerically much greater.

Arriving at #ESMO26 tomorrow just in time for what promises to be one of the most exciting sessions: Presidential Session #1. #INTerpath-001 presented by @ProfGLongMIA, #VOLGA by @tompowles1, #DeLLphi-305 by @sands_jacob & #DASLHiCaP by @niazi_Dr7. A terrific slate of discussants as well, incl @StephenVLiu (one of the most talented orators in our field, IMHO), @MichvdHeijden, @Silke_Gillessen & more. Hats off to @YJanjigianMD, @FAndreMD, @Prof_Nadia_H & #DrJamesLarkin for assembling a powerhouse program! @OncoAlert

🚨 #ESMO26 Lung Cancer: the 10 studies that best capture where the field is moving @OncoAlert What stands out to me from the @OncoAlert faculty selection is how much the lung cancer landscape is shifting toward smarter sequencing, biomarker-defined combinations, and more selective treatment intensification. 🫁 Top Ten from Madrid: 1️⃣ DeLLphi-305 — tarlatamab + durvalumab in 1L ES-SCLC maintenance 2️⃣ Krascendo 1 — divarasib vs sotorasib/adagrasib in KRAS G12C NSCLC 3️⃣ SAFFRON — osimertinib + savolitinib after osimertinib in EGFRm/MET+ disease 4️⃣ OptiTROP-Lung04 — sac-TMT after EGFR-TKI 5️⃣ OptiTROP-Lung06 — sac-TMT + pembrolizumab in PD-L1-negative NSCLC 6️⃣ PERSEE — pembrolizumab ± chemotherapy in PD-L1 ≥50% 7️⃣ SANOVO — savolitinib + osimertinib in 1L EGFRm/MET-overexpressed NSCLC 8️⃣ IFCT-2103 DIAL — continue pembrolizumab vs observation at 6 months 9️⃣ PANKU-Lung01 — iza-bren after third-generation EGFR TKI 🔟 SARON — consolidation RT in oligometastatic NSCLC 🎯 Why this matters: these studies are not just adding new drugs. They are refining when to intensify, when to combine, when to continue, and when biology should drive the next step. That is the real value of a “Top Ten” list: not more information — better prioritization of the data most likely to influence practice. @christine_lovly @GlopesMd @DrSanjayPopat @StephenVLiu @jillfeldman4 @UOzkerim @DrMirallas @CharuAggarwalMD @peters_solange @JordiRemon #lcsm #OncoAlert #ESMO26 #LungCancer #NSCLC #SCLC #PrecisionOncology

A new SoC in cisplatin ineligible muscle-invasive bladder cancer: The VOLGA Trial. Neoadjuvant Durva plus EV, without adjuvant EV. Less is more. #BladderCancer #ESMO26 @myESMO @sogug1 @_SEOM https://t.co/mkUEj73ADq

🚨 VOLGA: chemo-free durvalumab + enfortumab vedotin beat surgery alone in muscle-invasive #bladdercancer 🚨 @NEJM today 🧵1/2 👥 n=695, cisplatin-ineligible or declined MIBC 📊 Phase 3 RCT, 1:1:1 💊 Perioperative durva + EV vs durva + tremelimumab + EV vs radical cystectomy alone ⏱️ Estimates at 24 mo ✅ Durva + EV EFS 63.5% vs 45.1%, HR 0.51 (0.38-0.67), p<0.001 ✅ OS 78.4% vs 69.4%, HR 0.58 (0.40-0.83), p=0.003 ✅ Durva + treme + EV EFS HR 0.61 (0.47-0.80), but grade ≥3 AEs 79.5% vs 71.1% ⚠️ The 2 durvalumab arms were not compared head-to-head, so the CTLA-4 add is not clearly worth the added toxicity 🎯 Another cisplatin-free ADC + IO backbone for cisplatin-ineligible MIBC

🦉 Cancer Immunotherapy: A Week of Breakthroughs, Setbacks and New Biological Insights October 17–24, 2026 This week brought two major clinical advances: a personalized mRNA cancer vaccine significantly reduced melanoma recurrence, while a T-cell engager sharply extended survival in aggressive lung cancer. Other studies revealed why CAR-T cell quality, antigen presentation, and the tumor microenvironment can matter as much as immune activation itself. 🩸 1. A Personalized Cancer Vaccine Passes Its Biggest Test Moderna and Merck's individualized mRNA vaccine, intismeran autogene, reduced melanoma recurrence or death by 42% when combined with pembrolizumab in the Phase 3 INTerpath-001 trial. Among 1,137 patients with resected stage IIB–IV melanoma, two-year recurrence-free survival reached 82.2% versus 70.0% with pembrolizumab alone. Distant metastasis or death risk fell 38%, without a substantial increase in severe treatment-related toxicity. The results provide major randomized evidence that vaccines targeting patient-specific tumor mutations can improve clinical outcomes, not merely generate immune responses. Overall-survival data remain immature, and personalized manufacturing presents practical challenges. Source: https://t.co/FHlL1f9wPs 🩸 2. T-Cell Engagers Nearly Double Survival in Lung Cancer The Phase 3 DeLLphi-305 trial showed that adding Amgen's DLL3-targeted T-cell engager tarlatamab to durvalumab maintenance therapy extended median survival from 12.7 to 21.1 months in extensive-stage small-cell lung cancer. Among 563 patients, the combination reduced mortality risk by 58% and increased progression-free survival from 1.9 to 7.4 months. Tarlatamab recruits T cells directly to cancer cells, complementing durvalumab's PD-L1 blockade. The survival advantage is substantial, but cytokine-release syndrome occurred in 49.6% of patients, predominantly grade 1–2. Grade ≥3 treatment-related adverse events affected 20.9% versus 10.8%. These results could reshape first-line maintenance treatment, subject to regulatory review. Source: https://t.co/1TRq9VtseZ 🩸 3. Bladder Cancer Treatment Takes a Major Step Forward The Phase 3 VOLGA trial demonstrated a significant survival advantage with enfortumab vedotin plus durvalumab in patients with muscle-invasive bladder cancer unable or unwilling to receive cisplatin. Among 462 patients, the combination reduced the risk of progression, recurrence or death-related events by 49%. Two-year event-free survival reached 64% versus 45%, while overall survival was 78% versus 69%. The strategy combines targeted cytotoxic delivery through an antibody–drug conjugate with PD-L1 checkpoint inhibition. However, grade 3–4 adverse events occurred in 64% versus 44%. The results support a new perioperative option, although comparisons with other modern regimens remain unavailable. Source: https://t.co/VLXeYEzs9O 🩸 4. CAR-T Quality May Matter More Than Expansion A multicenter study involving 783 lymphoma patients found that CAR-T products enriched in naïve-like CCR7⁺CD45RA⁺ T cells were associated with significantly longer progression-free survival. In the primary cohort of 580 patients receiving axi-cel, these cells predicted better outcomes (HR 0.46; p=9.8×10⁻⁵), independently of tumor burden, inflammation and CAR-T expansion. An additional 203 patients confirmed the association. More previous treatment lines were linked to fewer naïve-like cells. The implication challenges a familiar assumption: expanding more CAR-T cells may be less important than preserving cells capable of sustained antitumor activity. Whether manufacturing changes that enrich these populations actually improve survival remains unproven. Source: https://t.co/GAN67wP3OV 🩸 5. A New Approach to Severe Immunotherapy Toxicity Researchers in Germany and Switzerland reported promising results using extracorporeal photopheresis to treat severe immune-related complications resistant to corticosteroids. The technique treats collected immune cells with a photosensitizing agent and ultraviolet light before returning them to circulation. In a prospective Phase 1b/2 study involving 30 patients, the response rate among evaluable inflammatory complications reached 96.3%, including responses in colitis, hepatitis and dermatitis. Treatment reduced inflammatory T-cell activity, including granzyme expression and interferon-γ/TNF signaling. No treatment-related serious adverse events occurred. The potential advantage is controlling dangerous inflammation without escalating systemic immunosuppression. However, the uncontrolled study cannot establish comparative efficacy or confirm preservation of antitumor immunity. Source: https://t.co/xDE6iBNXhy 🩸 6. Selective T-Cell Activation Shows Activity in Resistant Tumors Invikafusp alfa, an experimental bispecific antibody, activates selected T-cell populations expressing Vβ6 or Vβ10 T-cell receptors rather than broadly stimulating the immune system. In the Phase 1/2 START-001 trial, 4 of 27 patients (14.8%) treated at biologically optimal doses achieved objective responses, while 59.3% experienced disease control. Responses included microsatellite-stable colorectal cancer and PD-L1-negative lung cancer, where conventional checkpoint inhibition often has limited efficacy. The treatment expanded memory-like target T cells without broadly activating unrelated populations. This demonstrates preliminary clinical activity, not established benefit. Patient numbers remain small, durability is uncertain, and cytokine-release syndrome remains a risk. Source: https://t.co/2KupIGrKnT 🩸 7. Strong Vaccine Immunity Fails to Improve Pancreatic Cancer Outcomes The randomized Phase 2 AMPLIFY-7P trial tested camupepimut (ELI-002 7P), an off-the-shelf vaccine targeting mutant KRAS, in 144 patients with pancreatic cancer after standard treatment. Despite vaccine-specific T-cell responses in 98.9% of evaluable patients, the primary disease-free survival endpoint was missed: 23.8 versus 21.2 months (HR 0.85; p=0.5329). Subgroup analyses suggested possible benefit in patients without detectable circulating tumor DNA (HR 0.51) or prior radiotherapy (HR 0.59). The contrast is striking: nearly universal immune activation did not translate into a significant overall clinical benefit. Vaccination may work better against minimal residual disease, but subgroup signals remain exploratory and clinical efficacy is unproven. Source: https://t.co/18SHt23Nqc 🩸 8. Dual Checkpoint Blockade Targets Difficult Biliary Cancers Chinese investigators reported Phase 2 results for cadonilimab, a bispecific antibody blocking PD-1 and CTLA-4, combined with gemcitabine and cisplatin in advanced biliary tract cancer. Among 61 patients, the objective response rate reached 55.7%, with disease control in 85.2%. Median progression-free survival was 8.0 months and overall survival 15.6 months. Dual checkpoint blockade could provide broader immune activation than PD-1/PD-L1 inhibition alone. However, grade ≥3 adverse events occurred in 68.9%, including severe immune-related events in 18%. The single-arm design cannot establish superiority over approved chemoimmunotherapy. Randomized comparisons must determine whether increased immune stimulation produces a meaningful survival advantage. Source: https://t.co/aLKEXWZ2Vq 🩸 9. Tumors Can Hide Antigens Without Losing Them Researchers at Southern Medical University identified SMPD3, an enzyme involved in sphingolipid metabolism, as an unexpected regulator of tumor antigen presentation. In colorectal cancer models, increasing SMPD3 enhanced MHC-I expression at the cell surface without substantially increasing total MHC-I abundance. The mechanism involved intracellular trafficking rather than greater production of antigen-presenting proteins. SMPD3 overexpression increased CD8 T-cell infiltration, suppressed tumor growth in mice and improved experimental PD-1 blockade responses. This reveals another route to immune escape: cancer cells may retain antigen-presentation machinery but fail to deliver it to their surface. The findings are preclinical. SMPD3 is not yet a validated therapeutic target or clinical biomarker. Source: https://t.co/2J4IGGJiOI 🩸 10. Macrophages May Awaken Sleeping Cancer Cells French researchers uncovered a mechanism through which macrophages can reactivate dormant breast cancer cells. In three-dimensional tumor models, macrophage-derived MMP9 and lysyl oxidase (LOX) remodeled the surrounding extracellular matrix, activating EGFR/HER2 signaling and pushing dormant cancer cells toward renewed proliferation. Remarkably, this signaling occurred without conventional receptor-ligand activation. The finding links macrophage activity, tissue remodeling and metastatic recurrence through a mechanism distinct from classical checkpoint-mediated immune suppression. It raises the possibility that preventing relapse may require controlling the tumor's surrounding tissue environment, not just targeting residual cancer cells. The evidence comes from laboratory models. Its role in human metastatic recurrence and potential for therapeutic intervention remain unproven. Source: https://t.co/Z4TfhFEx9b

Day 2 (Presidential) #ESMO26 1. INTerpath001: mRNA vaccine in melanoma 2. VOLGA: Durva+EV in MIBC 3. DASLHiCaP: Dara+ADT+RT in Prost Ca 4. DeLLphi305: Tarla+Durva ES-SCLC #OncTwitter @myESMO #gusm #lcsm @OncoAlert @OncUpdates @DanaFarber @sands_jacob @tompowles1 1/5 https://t.co/Yu3s24fNTY https://t.co/yT1CxCZCYI

VOLGA Study – ESMO 2026, LBA2 Perioperative enfortumab vedotin (EV) plus durvalumab was evaluated in patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy. 2-year event-free survival (EFS): 64% vs. 45% (HR, 0.51). 2-year overall survival (OS): 78% vs. 69% (HR, 0.58). Pathological complete response (pCR): 45% vs. 10%. Perioperative EV plus durvalumab demonstrated substantial improvements in EFS and pathological complete response rates compared with the control arm. Overall survival outcomes also favored the treatment combination. Link : https://t.co/VHXbaw0MsV #ESMO2026 #VOLGAStudy #BladderCancer #EnfortumabVedotin #Immunotherapy

VOLGA tested for the 1st time a triplet with ADC + dual checkpoint inhibition in the neoadjuvant setting for cis-ineligible MIBC #ESMO26 3C of EV were associated with EFS, SG, pCR and ctDNA clearance. Time to talk about duration of therapy @OncoAlert 🔗https://t.co/4Cdc5CfIct https://t.co/4bUXsz7gLc https://t.co/pv2127GEMC

#ESMO26 Dr. Michiel van der Heijden discussed the implications of VOLGA alongside KEYNOTE-905 and KEYNOTE-B15: 🔹 EV + durvalumab doublet: EFS HR 0.51; OS HR 0.58, a 42% reduction in the hazard of death. 🔹 Triplet (+ tremelimumab): EFS HR 0.61; OS not yet significant. More toxicity, without a demonstrated advantage from CTLA-4 blockade. 🔹 Crucial difference: VOLGA used only 3 neoadjuvant cycles of EV, followed by RC and adjuvant durvalumab, without adjuvant EV. 🔹 The unresolved question: Which patients need adjuvant therapy? pCR is informative, but does not guarantee eradication of micrometastatic disease. 🚨Key message: The doublet is the regimen most likely to move forward. The next breakthrough may come from response-adapted treatment, not adding another drug. @UroToday @myESMO

#ESMO26 | VOLGA in cisplatin-ineligible MIBC: Durvalumab + enfortumab vedotin significantly improved: OS: HR 0.58 (p=0.0027) EFS: HR 0.51 (p<0.0001) 2-year OS: 78% vs 69%ctDNA clearance: 60% A major advance in MIBC@SCUColombia @achoHematoYOnco @myESMO @ASCO @OncoAlert @oncodaily https://t.co/Y1hvotHtif

Perioperative Durvalumab ± Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 VOLGA Trial @OncoAlert @tompowles1 #ESMO26 https://t.co/FJ8XJ2VcZP

VOLGA trial : The Arm1 - in MIBC, neoadjuvant Durvalumab + EV followed by surgery then adjuvant Durvalumab showed better EFS (NR vs 12 months HR 0.51) and OS (NR in both arms, HR 0.58) compared to the standard of care. #ESMO2026 @DrChoueiri @myESMO @darioT_ @E_de_Azambuja https://t.co/BzT5qzR5uY

🔊👏Bravo Dr Thomas Powles @TomPowles1 Outstanding Presentation @ Presidential Symposium, Topline Results VOLGA Trial, Perioperative durvalumab w/ or without tremelimumab + neoadj enfortumab vedotin in muscle-invasive bladder cancer #gusm #ESMO26 @OncoAlert https://t.co/eXZW8cMZYG

#ESMO26 @tompowles1 presents at the 👑presidential 👑 session VOLGA n=1009 phIII neoadjuvant #bladdercancer trial. 24mo EFS 63.5% vs 45% (HR 0.51), pCR 45% vs 10%. Triplet +tremelimumab hits EFS but not yet OS. #MIBC - @NEJM paper ➡️ ➡️ https://t.co/WlDvNeQGsc https://t.co/C8uRBpocLX

VOLGA marks a major step forward in cisplatin-ineligible MIBC. Perioperative durvalumab plus three cycles of neoadjuvant enfortumab vedotin reduced the risk of recurrence or death by nearly 50% and improved overall survival. ctDNA clearance was associated with substantially fewer recurrences. #ESMO2026 @tompowles1

🇬🇧 Brilliant to see @tompowles1 AGAIN on the podium, leading the way in bladder cancer! 🚨 Phase III VOLGA: ✅ 49% ↓ EFS events/death ✅ 42% ↓ risk of death ✅ 45% pCR vs 10% Fantastic UK & @NHSBartsHealth representation! 👏 #BladderCancer #VOLGA #ESMO2026 https://t.co/82e6xXLEcU

🔥 Presidential Symposium I #ESMO26 🗣️ @tompowles1 👉🏽 VOLGA phase 3, randomised, open-label trial, enrolled pts with MIBC (cT2-T4aN0/1M0 or cT1N1M0) ineligible for or refused cisplatin and were planned for RC 📌 EFS D+EV vs control: NR vs 12.1 HR 0.51 D+T+EV: NR (HR 0.61) 📌 OS D+EV vs control: 78 VS 69% at 24m HR 0.58 Triplet vs control: NS 📌 pCR Doublet vs control: 45 vs 8% 🩸ctDNA clearance impacts survival @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @brunolarvol 👇🏽👇🏽

VOLGA: perioperative EV + Durvalumab increases pCR, EFS and OS compared with cystectomy alone. A new standard option for these patients, in a setting that is becoming really crowded (NIAGARA, KN-905, KN-B15). #ESMO26 https://t.co/LdFwVrOXWH

Excellent presentation by @tompowles1! VOLGA: perioperative durvalumab + 3 cycles of neoadjuvant EV improved EFS (HR 0.51) and OS (HR 0.58) vs cystectomy ± adjuvant therapy in cisplatin-ineligible/declining MIBC. ADCs moving earlier! #ESMO26 @oncoalert @myESMO https://t.co/ex3NdpxzoI

Presidential symposium 1️⃣!! Volga trial: ph3 combo neoadjuvant EV + perioperative Durva +/- Treme. Dual primary endpoints of EFS were met. D+EV (HR 0.51) D+T+EV (HR 0.61) ❕#UrothelialCarcinoma #ESMO26 @myESMO @tompowles1 @FAndreMD https://t.co/HIeM2fM7L1

🆙#ESMO26 Presidential Symposium I 🔥VOLGA: Perioperative Durvalumab With or Without Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 Trial 🎙️ @tompowles1 🔢LBA2 🎯Durva+EV: Significantly Improved EFS (HR 0.51, 24-Mo 64% vs 45%) and OS (HR 0.58, p=0.0027) vs Control (n=233 vs 229) 🎯pCR 45% vs 10%; Durva+Treme+EV: EFS HR 0.61, OS Not Significant ☑️NCT04960709 🔗 https://t.co/t988kyrR7h @OncoAlert @Larvol @myESMO

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

With VOLGA results coming at #ESMO26, a summary of contemporary phase III perioperative trials in muscle-invasive bladder cancer. ⚠️ Different populations and designs—avoid cross-trial comparisons. VOLGA and EV-303 importantly include surgery-alone control arms without neoadjuvant therapy. 🔑 The next challenge: identifying who truly needs adjuvant ADC therapy—and who can safely avoid it. #BladderCancer #GUOnc @OncoAlert @BladderCancerUS

VOLGA (LBA2, #ESMO26): cisplatin-ineligible/refusing MIBC — neoadjuvant enfortumab vedotin + peri-op durvalumab vs control. Circulating figures (EV+durva arm): 2-yr EFS 64% vs 45% (HR 0.51); 2-yr OS 78% vs 69% (HR 0.58); pCR ~45% vs ~10%. Tremelimumab arm: EFS HR ~0.61, OS NS at interim. Absolute rates unverified — confirm at PS I (Powles). @tompowles1

💔 EV has a new partner! PEMBRO: “Another checkpoint inhibitor?!” 😳 EV: “We have survival data TOO!” ❤️ 🔥 VOLGA | ESMO 2026 EFS HR 0.51 | OS HR 0.58 But PEMBRO isn't out of the picture! KEYNOTE-905: EFS HR 0.40 | OS HR 0.50 Two promising perioperative partnerships in cisplatin-ineligible MIBC. ⚠️ Different trials. No head-to-head comparison. @myESMO @OncoAlert #MVOnco #ESMO2026 #BladderCancer

VOLGA (LBA2): perioperative durva ± tremelimumab + neoadjuvant EV vs cystectomy control in cisplatin-ineligible/refusing MIBC. 24-mo EFS 64% vs 45% with durva + EV, HR 0.51 (95% CI 0.38-0.67); 60% vs 45% with the triplet, HR 0.61 (95% CI 0.47-0.80). No trimodality arm. This doesn't answer the bladder-preservation comparison. #ESMO26 #radonc https://t.co/3skudJjr5t

ESMO 2026 - presidential LBA | VOLGA Phase III – Perioperative Durvalumab + Enfortumab Vedotin (EV) in cisplatin-ineligible/refusing patients: 📊 EV + Durva vs Control • 2-year EFS: 64% vs 45% (HR 0.51; p<0.0001) • 2-year OS: 78% vs 69% (HR 0.58; p=0.0027) • pCR: 45% vs 10% Adding tremelimumab improved EFS (HR 0.61) but no significant OS benefit yet, with higher grade 3/4 toxicity (42% vs 30%). 🔥can this stop the need of post op EV ? Probably yes . New SOC 🙂👍 Looking forward the full datasets @OncBrothers @OncoAlert @myESMO #ESMO26 #VOLGA #BladderCancer

🚨 #ESMO26 GU Oncology — the studies I would keep closest on the radar @OncoAlert What stands out from the @OncoAlert GU selection is how clearly the field is moving toward perioperative intensification, biomarker-driven treatment, smarter sequencing, and new mechanisms of action. 🟠 #BladderCancer VOLGA · KEYNOTE-B15 · ENERGIZE · KEYNOTE-866 🔵 #ProstateCancer DASL-HiCaP · CAPItello-281 · PROTEUS 🟢 #KidneyCancer LITESPARK-011 · LITESPARK-012 · ivonescimab · PE-PE · SWOG S2200 · XmAb819 🎯 Why this matters: these are not just isolated trial readouts. Together, they are redefining where we intensify, where we de-escalate, how we select patients, and how earlier disease settings are becoming increasingly systemic and biology-driven. For me, the most important question across all three tumors is the same: Who actually needs more treatment — and who can safely receive less? That is where GU oncology is heading. Proud to be part of this @OncoAlert faculty following the data closely at #ESMO26. @DrChoueiri @tompowles1 @neerajaiims @PGrivasMDPhD @TiansterZhang @AndreaNecchi @DrRanaMcKay @DrYukselUrun @crisbergerot @nataliagandur #OncoAlert #GUOncology #PrecisionOncology #CancerResearch

Lovely walking tour & sunset in Madrid @myESMO #ESMO26 Looking forward today to: #VOLGA peri-op durva/treme/EV MIBC & Daro in very high risk PCa both in presidential session🌟 #KNB15 ctDNA analysis Claudin-6 ADC in GCT #CAPITELLO281 capi OS in mCSPC NAT ICI in penile CA https://t.co/p31vBubCOj

✈️ En route to Madrid for #ESMO26, landing just in time for the data to start Friday morning. Most excited for: VOLGA LBA2 in bladder cancer, INTerpath-001's first phase 3 neoantigen win, LITESPARK-011 final in kidney cancer, and DASL-HiCaP in prostate. What a week ahead 🔬 #GUonc

🤩 @OncBrothers highlighting 🔑 studies presented on Day 1 of #ESMO26 #BreastCancer 1. #NATALEE 2. #HorizonBreast06 3. #TALENT #GIOnc 4. #RASolute302 5. #HerizonGEA01 #GUOnc 6. #KN866 7. #PEACE1 #OncTwitter #MedTwitter #bcsm #gism #gucsm @myESMO #MedX #MedEd #Oncology https://t.co/s1p1cmrz2k

#NATALEE at 6 years: sustained iDFS benefit with adjuvant ribociclib. iDFS: 83.2% vs 77.9%. OS favored ribociclib; nominal significance only, with descriptive analysis outside formal testing. Assoc. Prof. Nurullah İlhan #ESMO2026 #BreastCancer #OncoTwitter https://t.co/ghHUlehacF

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

🚨 #ESMO26 moves fast your inbox should help you keep up, not add more noise. @OncoAlert The daily @OncoAlert Newsletter is LIVE from Madrid 🇪🇸 and delivers the most relevant congress data straight to your inbox every morning. 📌 Day 1 highlights 🎗️ NATALEE 6-year OS 🧬 PANKU-Breast01 + Lancet publication 🟠 KEYNOTE-866 & ENERGIZE two important negative MIBC trials 🟣 HERIZON-GEA-01 3-year OS 🎯 Why this matters: congress coverage is not about reading everything. It is about identifying the data that deserve attention, understanding what they mean, and moving quickly from headline to clinical context. That is what @OncoAlert does best: Less noise. More signal. Science that matters. 🤝 For colleagues, by colleagues. 📩 Register FREE: https://t.co/NFi1ia680V 👉 Subscribe: https://t.co/kHfE8oDWmE @DrChoueiri @PGrivasMDPhD @AndreaNecchi @TiansterZhang @hoperugo @stolaney1 @christine_lovly @CathyEngMD @BenWestphalen @nataliagandur #OncoAlert #ESMO26 #Oncology #CancerResearch #MedicalEducation

🚨 Day 1 highlights from #ESMO26 are here! Subscribe for FREE 👉 https://t.co/Q2y6eL4mxY From NATALEE and PANKU-Breast01 to KEYNOTE-866, ENERGIZE & HERIZON-GEA-01 - stay updated with @OncoAlert, straight to your inbox every morning! 📩 https://t.co/ojhxebvmd6

#NATALEE OS is here. HR 0.81, 178 vs 205 deaths, 6-year OS difference 2.1%. monarchE was HR 0.84, 1.8% at 7 years. Two CDK4/6 inhibitors, two schedules, strikingly similar survival effect. The OS gap widens after ribociclib stops at year 3, as expected since deaths lag relapses. More importantly, the iDFS curve is still separating after treatment ended. And control patients who relapsed could get a CDK4/6i for metastatic disease, which should shrink the OS difference. The benefit held. What NATALEE adds over monarchE is N0, about 12% of the trial. The iDFS signal is there. N0 OS will be underpowered for a long time, so that conversation in clinic stays an iDFS conversation. #bcsm #ESMO26

🚨 ESMO 2026 | NATALEE: Positive OS at 6 yrs! 🔹 OS: HR 0.809 (95% CI 0.661–0.989), P=0.019 🔹 6-yr OS: 91.9% vs 89.7% (Δ 2.1%) 🔹 BCSS: HR 0.706 (~29% ↓ BC mortality) 🔹 iDFS/DDFS/DRFS: ~5% absolute benefit at 6 yrs 🔹 OS benefit generally consistent across subgroups 🔹 Post-recurrence CDK4/6i: 21% vs 44.4% Take-home: First positive OS results from NATALEE, supporting adjuvant RIB in HR+/HER2− EBC. #ESMO26 #NATALEE #BreastCancer #bcsm @OncoAlert

#ESMO26 | NATALEE: 6-year outcomes Adjuvant ribociclib + NSAI vs NSAI alone in eligible HR+/HER2− stage II–III EBC: ▪️ OS HR 0.809 (95% CI 0.661–0.989) Absolute 6-year benefit: 2.1 percentage points ▪️ IDFS HR 0.741 (95% CI 0.646–0.849) Absolute 6-year benefit: 5.3 percentage points Benefit persists with patients off ribociclib for a median of ~3 years. 𝘔𝘺 𝘬𝘦𝘺 𝘲𝘶𝘦𝘴𝘵𝘪𝘰𝘯: 𝘐𝘯 𝘤𝘭𝘪𝘯𝘪𝘤𝘢𝘭𝘭𝘺 𝘦𝘭𝘪𝘨𝘪𝘣𝘭𝘦 𝘱𝘢𝘵𝘪𝘦𝘯𝘵𝘴 𝘸𝘪𝘵𝘩 𝘭𝘰𝘸 𝘖𝘯𝘤𝘰𝘵𝘺𝘱𝘦 𝘋𝘟 𝘙𝘚 𝘢𝘯𝘥/𝘰𝘳 𝘭𝘰𝘸 𝘰𝘷𝘦𝘳𝘢𝘭𝘭 𝘳𝘦𝘤𝘶𝘳𝘳𝘦𝘯𝘤𝘦 𝘳𝘪𝘴𝘬, 𝘦𝘴𝘱𝘦𝘤𝘪𝘢𝘭𝘭𝘺 𝘕0 𝘥𝘪𝘴𝘦𝘢𝘴𝘦, 𝘪𝘴 𝘵𝘩𝘦 𝘢𝘣𝘴𝘰𝘭𝘶𝘵𝘦 𝘣𝘦𝘯𝘦𝘧𝘪𝘵 𝘭𝘢𝘳𝘨𝘦 𝘦𝘯𝘰𝘶𝘨𝘩 𝘵𝘰 𝘫𝘶𝘴𝘵𝘪𝘧𝘺 3 𝘺𝘦𝘢𝘳𝘴 𝘰𝘧 𝘳𝘪𝘣𝘰𝘤𝘪𝘤𝘭𝘪𝘣, 𝘤𝘰𝘯𝘴𝘪𝘥𝘦𝘳𝘪𝘯𝘨 𝘵𝘰𝘹𝘪𝘤𝘪𝘵𝘺, 𝘮𝘰𝘯𝘪𝘵𝘰𝘳𝘪𝘯𝘨 𝘣𝘶𝘳𝘥𝘦𝘯, 𝘢𝘯𝘥 𝘘𝘖𝘓? #BreastCancer #NATALEE

@Rodrosb @myESMO I see the benefit in high-risk, node-positive patients, especially after the NSABP B-42 data presented at #ESMO26. However, I have more doubts about the N0 population in NATALEE. Great topic!@Rodrosb

NATALEE 6-y results are out! #ESMO26 2.1 delta in survival at 6 years. Thanks @Annals_Oncology for reporting subsequent therapy data! 👉Only 44.4% of control arm patients with distant recurrence received a first-line CDK4/6i Does this survival difference truly inform clinical practice in settings where CDK4/6i are standard of care for metastatic disease? In my opinion, the answer is no.

Great news! NATALEE is positive for overall survival. Great presentation from Dr Slamon. Big thanks to all the patients, and research nurses who risked themselves during COVID to make this study a success. #ESMO26 #ESMO2026 https://t.co/eqTqJ8Mg83

NATALEE: 6-Year Update at #ESMO26 Adjuvant ribociclib + NSAI continues to improve iDFS in HR+/HER2− early breast cancer, with updated data showing an OS benefit (HR 0.81; 95% CI, 0.66–0.99) and improved #BreastCancer –specific survival. @OncoAlert #bcsm @myESMO https://t.co/MUiDWRxCjG

Cowabunga! 🌊 Riding the Early & Adjuvant Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 NATALEE, 6 yrs: ribociclib overall survival hazard ratio 0.81, +2.1%. Encouraging, concordant, consistent. But: no alpha, nominal p, fragility ~2–3 deaths. @OncoDaily #OncoDailyAmbassador @OncoAlert

@myesmo #ESMO26. The start to an exciting meeting - first two oral BC sessions today. The first session with OS data from Natalee, long term benefit from extended letrozole in B42, huge benefits from 3 novel ADCs in HER2 low/HR+ & Talent. @OncoAlert https://t.co/NsYeBeQYPH

#ESMO26 Natalee 6 year data with improvement in OS including in node negative & no prior chemo patients - with online publication in @Annals_Oncology #bcsm #ESMOAmbassadors @OncoAlert https://t.co/ABh6KQBC7R

Oral abstract #BreastCancer session at #ESMO26: updated data from NATALEE trial simultaneously published in @Annals_Oncology @OncoAlert @myESMO https://t.co/ZwJZGrPrL0

Maintained iDFS benefit (Δ 5.3%) and favorable OS (Δ 2.1%) with adjuvant ribociclib after 6 years of follow up (all patients off ribo). Efficacy comparable to abema (monarchE), with different toxicity profile and wider population (N+ and high-risk N0). #ESMO26 #ESMOAmbassadors https://t.co/VeVCp7QDGi

NATALEE 6-year OS analysis shows modest (early…given what we just saw in NSABP42…) improvement in OS. IDFS benefit persists over time. #ESMO26 @OncoAlert https://t.co/sNIIKpV3aG

NATALEE 6-year analysis demonstrated an OS benefit with adjuvant ribociclib in HR+/HER2− early breast cancer (HR 0.81; absolute benefit 2.1%), with sustained iDFS benefit (HR 0.74; absolute benefit 5.3%). #ESMO26 https://t.co/t6AYUyKOeU

6-year results of Natalee (ribociclib): improvements in OS, BCSS, iDFS, DRFS - some subgroups analyses still required #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO @Annals_Oncology https://t.co/acLnDZoxka

One of the most awaited abstracts of #ESMO26: OS results of the NataLEE trial Adjuvant ribociclib provides statistically significant ⬆️ OS: delta of 1.2% at 60 months and 2.1% at 72 months (6-years) Confirmed and sustained benefit in IDFS, DDFS and DRFS @OncoAlert https://t.co/XMjNQqwtJH

NATALEE: OS data Adjuvant ribociclib in ER+ breast cancer 6 yr OS HR 0.809 (delta 2.1%) BCSS: 0.706 (delta 2.6%) 6 yr iDFS HR 0.741 (delta ~5%) DDFS: HR 0.744 @OncoAlert #ESMO26

Today at #ESMO26, the 6-year results of NATALEE will be presented. Ahead of the presentation, my personal view on the survival gains with adjuvant CDK4/6 inhibitors… The 6-year OS rates in NATALEE were 91.86% vs 89.73%: an absolute gain of 2.1 percentage points (HR 0.809; 95% CI 0.661–0.989; nominal one-sided p=0.019). The absolute 7-year OS gain in monarchE was 1.8 percentage points (HR 0.842; p=0.027). I do not think these gains should be dismissed as “only 2%.” In the EBCTCG analysis, adding taxanes to anthracycline-based chemotherapy—an approach we have accepted as standard for years—provided an absolute 5-year OS gain of approximately 1.9 percentage points. The populations and follow-up periods differ, so we cannot directly compare treatment efficacy. However, the standards we use to judge a few percentage points of survival benefit should be consistent. Moreover, 95.4% of patients in monarchE had already received chemotherapy. This survival gain represents an additional benefit on top of chemotherapy and endocrine therapy. Patient selection, toxicity, treatment duration, and cost certainly deserve discussion. However, the survival benefit of adjuvant CDK4/6 inhibitors in appropriately selected patients should not be underestimated.

NATALEE OS: no formal significance; the analysis is descriptive (nominal P, no alpha). monarchE, by contrast, had a prespecified alpha-controlled OS analysis and met it. NATALEE: HR ~0.80 stable, Δ2.1%, BCSS supportive. Clinically meaningful, not confirmatory. #ESMO26 #NATALEE #MonarchE

NATALEE at 6 years: Ribociclib + NSAI vs NSAI alone in HR+/HER2− early breast cancer: • 6-year OS: 91.86% vs 89.73% • OS HR 0.809 (95% CI 0.661–0.989); nominal 1-sided P=0.019 • Absolute OS benefit: 2.1% • 6-year iDFS: 83.23% vs 77.92% • iDFS HR 0.741 (95% CI 0.646–0.849) • Absolute iDFS benefit: 5.3% Is OS significant? Looking forward to full data .@Timothee_MD @myESMO @OncBrothers @OncoAlert #ESMO26 #BreastCancer #NATALEE

🤩 @OncBrothers highlighting 🔑 studies presented on Day 1 of #ESMO26 #BreastCancer 1. #NATALEE 2. #HorizonBreast06 3. #TALENT #GIOnc 4. #RASolute302 5. #HerizonGEA01 #GUOnc 6. #KN866 7. #PEACE1 #OncTwitter #MedTwitter #bcsm #gism #gucsm @myESMO #MedX #MedEd #Oncology https://t.co/s1p1cmrz2k

NATALEE, NSABP B-42, PANKU-Breast01, TALENT, HERIZON-GEA-01, KEYNOTE-866 ve RASolute-302. Sağkalım faydası nerede gösterildi? Hangi çalışma primer sonlanımını karşılayamadı? Yeni verileri hasta grubu ve tedavi bağlamıyla birlikte değerlendirdik. #ESMO2026 https://t.co/gsMeDN50vu

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

Overall Day 1 message in bladder cancer: Not all perioperative IO strategies are equal. Adding PD-1/PD-L1 inhibitors to cisplatin-based chemotherapy has now failed in two large Phase 3 trials (KEYNOTE-866 and ENERGIZE), while EV + pembrolizumab-based approaches (and NIAGARA) have succeeded. Biomarker selection is increasingly important. @myESMO @OncoAlert @OpenMedicineHQ @tompowles1 @AndreaNecchi @Uromigos @urologysummit #ESMO26

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

🚨 Perioperative immunotherapy in MIBC at #ESMO2026. Three phase III trials, three different answers, and one uncomfortable lesson for those of us who report pCR. 🔬 📊 NIAGARA (durvalumab + GC, n=1,063): pCR 37.3%, EFS HR 0.68 (0.56–0.82), OS HR 0.75 (0.59–0.95) ✅ 
📊 KEYNOTE-866 (pembrolizumab + GC, n=907): pCR 44.4%, EFS HR 0.88 (0.71–1.10), OS HR 1.00 (0.76–1.27) ❌ 
📊 CA017-078 (nivolumab + GC, n=653): pCR 39.1%, EFS HR 0.94 (0.71–1.25), OS HR 0.88 (0.64–1.21), OS immature ❌ Cross-trial, not head to head. Populations, schedules, follow-up (34 to 55 months) and statistical design all differ, so the ranking is exploratory. But look at the direction. The trial with the highest pCR returned an OS hazard ratio of exactly 1.00. 🧠 Three points from the pathology side: 1️⃣ pCR is a response marker, not a surrogate. Comparable absolute pCR gains of roughly 9 to 10 points across all three, divergent survival. If pCR tracked cure, that pattern should not be possible. pCR remains elusive at least for standard chemotherapy plus IO. 2. And pCR itself is not standardised across trials. ypT0N0 depends on sampling protocol, block numbers, regression assessment and whether review is central or local. The NIAGARA figure quoted here comes from a reanalysis, which tells you the endpoint moved on re-review. A 9-point difference is not comfortably above that measurement noise. Also worth noting: NIAGARA and KEYNOTE-866 both gave adjuvant IO, CA017-078 did not. So adjuvant continuation alone does not explain the split either. We genuinely do not know why these diverged. 🎯 Which is the real message. We are comparing trials on an endpoint we produce, that is not validated, not standardised, and not stratified by biology. Fixing that is a pathology job, and it is overdue. We need that now more than ever with neoadjuvant systemic phase becoming SOC. @OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot #Uropathology #BladderCancer #blcsm #MIBC #pathtwitter Great summary below from Niklas Klümper.

🚨 Day 1 highlights from #ESMO26 are here! Subscribe for FREE 👉 https://t.co/Q2y6eL4mxY From NATALEE and PANKU-Breast01 to KEYNOTE-866, ENERGIZE & HERIZON-GEA-01 - stay updated with @OncoAlert, straight to your inbox every morning! 📩 https://t.co/ojhxebvmd6

Nice comparison chart @tompowles1 — control cohorts in the #ENERGYZE & #Keynote866 trials both did much better than #NIAGARA control cohort… some may have had access to adjuvant IO to contribute to EFS? #ESMO26 @myESMO @OncoAlert https://t.co/K6ubio90xc

#ESMO26 🚨 KEYNOTE-866: The final EFS analysis (N=907) of perioperative pembrolizumab + cisplatin/gemcitabine vs chemotherapy alone: 🔹 5-year EFS: 63.5% vs 61.9% (HR 0.88; p=0.137) 🔹 5-year OS: 70.8% vs 70.9% (HR 1.00) 🔹 pCR: 44.4% vs 35.8% 🔹 Grade 3–5 AEs: 80.2% vs 75.1% Despite a numerically higher pCR rate, no significant EFS benefit emerged, and OS was virtually identical. 🚨In an evolving perioperative MIBC landscape, KEYNOTE-866 does not support adding pembrolizumab to cisplatin/gemcitabine. @urotoday @myESMO

🎯 Starting the GU oral session! #ESMO26 @JensBedke presented the ph3 study in MIBC KN-866 A negative study of Cis-Gem + Pembro vs Cis-Gem periop.🤷‍♂️ What about NIAGARA study? 🤨 @OncoAlert @myESMO @DrFelixGuerrero @GuardConsortium @UroTarget https://t.co/dYEYe4TBwq

Excellent presentation by Jens presenting results from KN866 trial that did not meet its primary endpoint in contrast with NIAGARA. Peri-op EV-pembro is the SOC in MIBC, awaiting VOLGA trial tomorrow! @myESMO #ESMO26 #ESMOAmbassadors @OncoAlert @Uromigos @shilpaonc @AndreaNecchi https://t.co/pDpZgq4etv https://t.co/dB1E6AlrWF

Two periop cis gem based phase 3 trials, adding a PD-1 to neoadjuvant cis-gem in MIBC did not improve EFS. 📉 KEYNOTE-866 pembro: EFS HR 0.88, OS HR 1.00 📉 CA017-078 nivo: EFS HR 0.94, pCR 39.1% vs 29.6% missed sig 🔍 Both continued the PD-1 after cystectomy, 13 cycles of pembro and 9 of nivo ctDNA was prognostic in but did not enrich for who benefited #ESMO26 #BladderCancer #MIBC #GUonc

5 phase III perioperative MIBC trials, with differing results. EV-303, EV-304 and NIAGARA improved EFS/OS, while ENERGIZE and KEYNOTE-866 did not meet their EFS endpoints. Important differences in patient populations, regimens and trial design. Cross-trial comparisons require caution. #ESMO26 @OncoAlert

ENERGIZE: perioperative CisGem +/- Nivo in MIBC. No improvement in survival endpoints, just like KN-866. Food for thought… #ESMO26 https://t.co/WvI1UDVNMD

Negative Ph.III KEYNOTE-866 by #DrJensBedke: perioperative pembrolizumab + neoadjuvant Gem/Cis vs placebo + Gem/Cis in cis-eligible MIBC. EFS HR 0.88 (95% CI 0.71-1.10), p=0.137. pCR 44.4% vs 35.8%; OS HR 1.00. Higher pCR did not translate into EFS benefit. #ESMO26 #BladderCancer @myESMO @OncoAlert

KEYNOTE-866: Negative for EFS. ENERGIZE: Negative for EFS. → What made the difference between these trials and NIAGARA? #ESMO26 https://t.co/vqu0TprzZx

#ESMO26 Adding perioperative pembro to Gem/Cis did not significantly improve EFS in cis-eligible MIBC (HR 0.88) in KN866. Higher pCR rates (although not formally tested) were seen in the pembro arm. More info in the concomitant publication in @Annals_Oncology @OncoAlert https://t.co/Ls5WRv4BJP

KEYNOTE-866 did not show EFS not OS. Great presentation 👏🏼by Prof Jens Bedke #ESMO26 @OncoAlert @Uromigos @urotoday @Uroweb @DGUrologie @high5md https://t.co/h2WiciZeJF

Full house for Bladder/RCC updates first with #KN866 #ESMO26 Gem/cis in MIBC + placebo or pembro (➖) study & less relevance in the era of EVP SOC Vs similar trial NIAGARA was ➕ pCR 44.4% vs 35.8% EFS & OS not significant We wait #VOLGA tomorrow for more in this space https://t.co/uSLgxYSoMO

🚨⭐ #ESMO26 |Abstract 4735O KEYNOTE-866 🟠 Perioperative pembrolizumab or placebo + neoadjuvant cisplatin and gemcitabine in muscle-invasive bladder cancer: Phase III KEYNOTE-866 🎤 Presented by Jens Bedke 🇩🇪 @OncoAlert 🔬 Can adding perioperative pembrolizumab to cisplatin-based neoadjuvant chemotherapy improve outcomes in cisplatin-eligible MIBC? 📊 STUDY DESIGN Phase III, randomized, double-blind, placebo-controlled trial. 👥 N=907 patients with cisplatin-eligible MIBC. 🔹 Pembrolizumab + gemcitabine/cisplatin → radical cystectomy → adjuvant pembrolizumab (n=453) 🔹 Placebo + gemcitabine/cisplatin → radical cystectomy → adjuvant placebo (n=454) Median follow-up: 60.9 months. 📊 KEY RESULTS ❌ Event-free survival (PRIMARY ENDPOINT) • Median EFS: 74.1 months vs NR • HR 0.88 (95% CI 0.71–1.10) • p=0.1366 ➡️ No statistically significant EFS improvement. 📈 Pathological complete response (pCR) ✅ 44.4% vs 35.8% • Estimated difference: +8.9 percentage points (95% CI 2.5–15.1). ⚠️ Higher pCR did NOT translate into a statistically significant improvement in the primary EFS endpoint. 📊 Overall survival • Median OS: NR in both arms • HR 1.00 (95% CI 0.79–1.27) ➡️ No observed OS advantage. pCR and OS were not formally tested for statistical significance under the hierarchical testing strategy. 🏥 Surgery • Underwent cystectomy: 91.6% vs 87.9%. ⚠️ SAFETY • Grade 3–5 treatment-emergent AEs: 80.2% vs 75.1%. • Grade 3–5 immune-mediated AEs/infusion reactions: 8.9% vs 1.8%. 🔬 CONCLUSION KEYNOTE-866 did not meet its primary EFS endpoint. Despite increased pCR rates, perioperative pembrolizumab added to neoadjuvant cisplatin/gemcitabine did not demonstrate a significant EFS benefit. ⭐ MY POINT OF VIEW | CLINICAL PEARL A higher pathological response rate is encouraging, but it is not enough to redefine a standard of care. In curative-intent MIBC, durable disease control and survival must drive treatment decisions. 📌 These findings do not support routinely adding perioperative pembrolizumab to neoadjuvant gemcitabine/cisplatin in cisplatin-eligible MIBC. 💡 More treatment does not necessarily mean better outcomes. The real challenge is identifying which patients benefit from intensification—and which do not. 🌍 GU Oncology Community @urologysummit @gbanna74 @ravikanesvaran @PGrivasMDPhD @tompowles1 @apolo_andrea @sonpavde @montypal @DrChoueiri @neerajaiims @HHammersMD @TiansterZhang @drenriquegrande @crisbergerot @DrDanielHeng @Silke_Gillessen @EfstathiouEleni @BraunMDPhD @brian_rini @AOmlin @DrYukselUrun @yekeduz_emre @cdanicas @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #MIBC #GUOncology #ClinicalTrials #OncoAlertAF

🚨 Negative results from KEYNOTE-866 at #ESMO26. Perioperative pembrolizumab added to neoadjuvant gemcitabine/cisplatin failed to significantly improve event-free survival in muscle-invasive bladder cancer (HR 0.88; 95% CI 0.71–1.10; P=0.1366). #BladderCancer https://t.co/QzbD5VUnK6

#ESMO26 Keynote 866 in muscle invasive bladder cancer no difference in EFS. More pCR than chemo alone @SCUColombia @achoHematoYOnco @myESMO @ASCO @OncoAlert @oncodaily https://t.co/aoNd2Bbkqt

#ESMO26 Day 1 has arrived! Follow along with @OncoAlert for full coverage! Highlights from the GU Renal & Urothelial Proffered Paper Session today: 🔴 Ph 3 KEYNOTE-866 (GC +/- perioperative pembro in MIBC) 🔴 Ph 3 ENERGIZE (GC +/- perioperative nivo in MIBC) 🔴 Ph 1 TROPHYU-01 Cohort 7 (SG + EV + Zim in 1L La/mUC) 🔴 ctDNA analyses from Ph 3 KEYNOTE-B15 (EV+P vs GC in cis-eligible MIBC) Key❓: Why were KN-866 and ENERGIZE negative while NIAGARA was positive? @scocmem @nataliagandur @DrKarineTawagi @niklas_kluemper @OncoAlert

#ESMO2026 🚨 Three phase III trials with perioperative chemoimmunotherapy. Different outcomes in MIBC. NIAGARA: durvalumab + GC → EFS HR 0.68, OS HR 0.75 ✅ KEYNOTE-866: pembrolizumab + GC → EFS HR 0.88, OS HR 1.00 CA017-078: nivolumab + GC → EFS HR 0.94 Interestingly, all three showed numerically higher pCR rates, but only NIAGARA demonstrated statistically significant survival benefits in the reported analyses. Why? Differences in trial populations, treatment schedules, statistical design—or tumor biology? These are cross-trial observations, not head-to-head comparisons. We should resist attributing the differences simply to PD-1 versus PD-L1 inhibition. The key challenge: identifying which MIBC patients truly benefit from adding immunotherapy to chemotherapy. We urgently need predictive biomarkers and molecularly informed perioperative treatment selection. 🔬 @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot @Markuseckstein3

🌟Context: EV + pembro already moved the bar perioperatively. 🧵2/2 🔑KEYNOTE-905/EV-303 (cisplatin-ineligible, vs surgery): EFS HR 0.40, pCR 57% vs 9% 🔑KEYNOTE-B15/EV-304 (cisplatin-eligible, vs cis-gem): EFS HR 0.53, OS HR 0.65 👉VOLGA adds a chemo-free durva + EV option to that landscape. 🔗 https://t.co/TMEcrvUZOM @LauraBukavinaMD @UroOnc @urotoday @UrologyTimes @myESMO @DrJJZhang @AmandaNizamMD @jgong15 @UCLAHealthJCCC @Uro_Oncologist

Elegant presentation by @Uro_Oncologist reporting HRQoL from #Keynote-B15. Perioperative EV-P was not associated with clinically meaningful detriment in general HRQoL or cystectomy-specific HRQoL ! #ESMO26 #Day2 @myESMO @OncoAlert https://t.co/eSoiNht3Jw

#ESMO26 KEYNOTE-B15 HRQoL results further support perioperative EVP in MIBC No clinically meaningful differences in HRQoL despite improved EFS and OS. The greatest deterioration occurred in both arms after surgery (sexual dysfunction) Congrats @Uro_Oncologist! @OncoAlert https://t.co/kPW3DFTBMv

🎯 #ESMO2026 2º day Rapid oral GU non-prostate session. @Uro_Oncologist presented the HRQL of EV-304 periop MIBC!! EV +pembro was not associated with a clinically meaningful detriment in general HRQoL or cystectomy-specific HRQoL!! @OncoAlert @myESMO @GuardConsortium @DrChoueiri @tompowles1 @urotoday @PGrivasMDPhD

Circulating LBA — confirm at PS I (Powles). What is solid across multiple posts: EFS HR ~0.51, OS HR ~0.58. Absolute 2-yr rates differ by source; treat as unverified until slides. Open question after EC EV + pembrolizumab (EV-304/KN-905): how does neoadjuvant-only EV + peri-op durvalumab sit next to peri-op EV + pembro as today’s SoC?

#ESMO26 Exploratory ctDNA findings from phase III KEYNOTE-B15, comparing perioperative EV+pembrolizumab vs cisplatin/gemcitabine. Key findings: 📌Presurgical ctDNA clearance: 82.1% vs 66.7% 📌24-month EFS after ctDNA clearance: 81.1% vs 63.2% 📌Persistent ctDNA positivity: 24-month EFS only ~33–35% 📌Postsurgical ctDNA positivity: Only 10% event-free at 24 months in either arm 📌Presurgical ctDNA-negative patients: pCR 72.4% vs 43.7% @UroToday @myESMO

Is ctDNA becoming indispensable in muscle-invasive bladder cancer? KEYNOTE-B15 at #ESMO2026 reinforces its prognostic value and shows higher ctDNA clearance with EV + pembrolizumab (82.1% vs 66.7%). The ? is no longer whether ctDNA matters, but how to integrate it in practice. https://t.co/sz8PLGyzOp

KEYNOTE-B15 ctDNA analysis presented by Jonathan Chatzkel at #ESMO26, with Min Teo as discussant 🧬 In cisplatin-eligible MIBC, ctDNA+ before surgery meant almost no pCR with either regimen (3.7% with EV + pembro, 2.2% with cis/gem). Among ctDNA− patients, pCR was 72.4% with EV + pembro vs 43.7% with cis/gem. In the EV + pembro arm, patients who cleared ctDNA had 24-month EFS of 81% vs 33% with persistent ctDNA+. The postsurgery results replicate NIAGARA. Serial ctDNA could open the door to bladder-sparing and surveillance questions. #MRD #ctDNA #BladderCancer

ctDNA is a risk signal, not yet a treatment compass? KEYNOTE-B15: clearance 82.1% vs 66.7% with EV/pembro vs chemo. When can we safely act on it? @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 @tompowles1 @urologysummit @isliquidbiopsy

KEYNOTE-B15 ctDNA analysis, cis-eligible MIBC: EV plus pembro cleared ctDNA more often than cis-gem. 📈 Presurgery ctDNA negative: pCR 72.4% vs 43.7% 📊 24-month EFS if cleared 81.1% vs 63.2%, if ctdna persistent 33.3% vs 35.3% 🔍 Presurgery ctDNA positive: pCR only in 2 of 72 across both arms ctDNA is prognostic in both arms. Persistent positivity does poorly on either regimen, and know seeing trial designs to address. #ESMO26 #BladderCancer #MIBC #ctDNA #GUonc

🚨⭐🟠 #ESMO26 | Abstract 4734O | KEYNOTE-B15 / EV-304 ctDNA Analysis of the Phase III KEYNOTE-B15 Trial: Neoadjuvant and Adjuvant Enfortumab Vedotin + Pembrolizumab in Cisplatin-Eligible Muscle-Invasive Bladder Cancer 🎤 Presented by Jonathan Chatzkel 🇺🇸 | Moffitt Cancer Center @OncoAlert @urologysummit 🧬 Can molecular response help redefine perioperative treatment in MIBC? 🔬 STUDY DESIGN Phase III KEYNOTE-B15/EV-304 | N=808 🟢 Perioperative EV + pembrolizumab (n=405) 🔴 Neoadjuvant gemcitabine/cisplatin followed by observation (n=403) All patients underwent planned radical cystectomy + PLND. Exploratory ctDNA analysis using the tumor-informed Signatera assay at baseline, presurgery, postsurgery and during adjuvant treatment. 📊 KEY RESULTS 🧬 1️⃣ Baseline ctDNA: a powerful prognostic marker ctDNA positivity was associated with worse EFS. EV + pembrolizumab vs chemotherapy: ✅ Baseline ctDNA-positive: HR 0.54 (95% CI 0.37–0.80) ✅ Baseline ctDNA-negative: HR 0.68 (95% CI 0.37–1.26) 📌 EFS estimates favored EV + pembrolizumab in both subgroups, although the CI crossed 1 in ctDNA-negative patients. 🧬 2️⃣ ctDNA CLEARANCE BEFORE SURGERY ✅ EV + pembrolizumab: 82.1% 🔴 Gemcitabine/cisplatin: 66.7% 📈 Absolute difference: +15.4 percentage points. Molecular clearance was associated with more favorable EFS and pathological response. 🔬 3️⃣ pCR BY PRESURGICAL ctDNA STATUS Among patients who were ctDNA-negative before surgery: ✅ EV + pembrolizumab: 72.4% 🔴 Gemcitabine/cisplatin: 43.7% Among those remaining ctDNA-positive: • EV + pembrolizumab: 3.7% • Chemotherapy: 2.2% 📌 Persistent ctDNA positivity identified patients with a very low probability of pCR. 🧬 4️⃣ POSTSURGICAL ctDNA AND EFS EV + pembrolizumab vs chemotherapy: ✅ ctDNA-negative: HR 0.48 (95% CI 0.29–0.81) 🔹 ctDNA-positive: HR 0.63 (95% CI 0.30–1.35) Postoperative ctDNA positivity was associated with particularly poor EFS. ⚠️ Interpretation requires caution: the postsurgical ctDNA-positive subgroup was small, and sample availability decreased over time. 🔬 CONCLUSIONS ✅ ctDNA positivity identifies patients with poorer prognosis. ✅ ctDNA clearance was higher with EV + pembrolizumab than with cisplatin-based chemotherapy. ✅ Molecular clearance correlated with improved pathological response and EFS. ✅ EFS estimates favored EV + pembrolizumab across ctDNA-defined groups. ⭐ MY POINT OF VIEW | CLINICAL PEARL We are moving beyond pathological response toward molecular assessment of treatment effectiveness. 🧬 ctDNA could become an essential tool for perioperative risk stratification in MIBC. But an important distinction remains: Prognostic ≠ Predictive. These findings do not yet establish ctDNA as a biomarker for selecting EV + pembrolizumab, omitting cystectomy or safely de-escalating adjuvant therapy. 💡 The next breakthrough may not be another treatment combination, but learning how to personalize treatment intensity according to molecular response. 📌 Prospective ctDNA-guided trials will be essential to translate molecular clearance into clinical decisions. 🌍⭐ GU ONCOLOGY COMMUNITY @brian_rini @tompowles1 @declangmurphy @KidneyCancer @salvolarosa @RenuEapen @seanmcbride @DrJaVallejo @crisbergerot @DrDanielHeng @apolo_andrea @DrChoueiri @PGrivasMDPhD @TiansterZhang @HHammersMD @neerajaiims @amerseburger @sonpavde @drenriquegrande @scserendipity1 @Silke_Gillessen @EfstathiouEleni @BraunMDPhD @cdanicas @AOmlin @montypal @gbanna74 @ravikanesvaran @Uromigos @gu_onc @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #MIBC #ctDNA #GUOncology #PrecisionOncology #OncoAlertAF

KEYNOTE-B15 ctDNA analysis: Only 4.8% of patients remained ctDNA-positive after neoadjuvant EV + pembrolizumab and radical surgery. ctDNA-guided treatment strategies may become increasingly important in the EV + pembrolizumab era. #ESMO26 https://t.co/me0gaXLX8V

Interesting ctDNA analysis from #EV304/B15 trial — ctDNA (+) groups w poor prognosis but EV-pembro works regardless of ctDNA status @myESMO #ESMO26 @oncoalert https://t.co/CoJhNDucjN

5 phase III perioperative MIBC trials, with differing results. EV-303, EV-304 and NIAGARA improved EFS/OS, while ENERGIZE and KEYNOTE-866 did not meet their EFS endpoints. Important differences in patient populations, regimens and trial design. Cross-trial comparisons require caution. #ESMO26 @OncoAlert

#ESMO26 Day 1 has arrived! Follow along with @OncoAlert for full coverage! Highlights from the GU Renal & Urothelial Proffered Paper Session today: 🔴 Ph 3 KEYNOTE-866 (GC +/- perioperative pembro in MIBC) 🔴 Ph 3 ENERGIZE (GC +/- perioperative nivo in MIBC) 🔴 Ph 1 TROPHYU-01 Cohort 7 (SG + EV + Zim in 1L La/mUC) 🔴 ctDNA analyses from Ph 3 KEYNOTE-B15 (EV+P vs GC in cis-eligible MIBC) Key❓: Why were KN-866 and ENERGIZE negative while NIAGARA was positive? @scocmem @nataliagandur @DrKarineTawagi @niklas_kluemper @OncoAlert

🚨 Important new ctDNA data from KEYNOTE-B15 at ESMO 2026! In cisplatin-eligible MIBC, EV+pembrolizumab achieved: 🔹 82.1% ctDNA clearance during neoadjuvant treatment vs 66.7% with gemcitabine/cisplatin. 🔹 87.0% ctDNA negativity before surgery vs 80.3% with chemotherapy. 🔹 95.2% ctDNA negativity after cystectomy vs 86.5% with chemotherapy. Strikingly, only 4.8% remained ctDNA-positive after neoadjuvant EV+pembrolizumab and surgery! We know from IMvigor011 that postoperative ctDNA can identify patients at high risk of recurrence and help guide adjuvant treatment strategies. But what about patients achieving both pCR and sustained ctDNA negativity? Do they really need another 5–6 cycles of adjuvant EV, with the potential for cumulative tox/ neuropathy? Could pCR + ctDNA clearance, followed by longitudinal ctDNA monitoring, define a population suitable for treatment de-escalation? VOLGA will add another important piece to this puzzle, using only 3 neoadjuvant EV cycles without adjuvant EV. Of course, neither KEYNOTE-B15 nor VOLGA can establish the necessity of adjuvant EV through cross-trial comparisons. We urgently need prospective, biomarker-guided de-escalation trials—not simply more treatment for everyone. @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot @Markuseckstein3

Lots of exciting developments at #ESMO26! Several important studies were also published simultaneously in major medical journals. A few highlights: 1. Small-cell lung cancer (NEJM): Adding tarlatamab to first-line durvalumab maintenance improved median overall survival from 12.7 to 21.1 months in the phase 3 DeLLphi-305 trial. 2. HER2-positive breast cancer (NEJM): Anbenitamab, a HER2-targeted bispecific antibody, plus HB1801 improved 24-month progression-free survival to 58.5% vs 34.4% with standard therapy (HR 0.46). 3. Muscle-invasive bladder cancer (NEJM): Perioperative durvalumab plus neoadjuvant enfortumab vedotin improved 24-month event-free survival to 63.5% vs 45.1% with surgery alone. 4. HR-positive, HER2-negative breast cancer (Lancet): The EGFR/HER3-targeted bispecific antibody-drug conjugate izalontamab brengitecan doubled median progression-free survival versus chemotherapy (8.2 vs 4.0 months; HR 0.41) in the phase 3 PANKU-Breast01 trial. 5. Melanoma (Nature Medicine): Five-year RELATIVITY-047 results showed sustained overall survival benefit with nivolumab + relatlimab vs nivolumab alone (HR 0.78). Full publications below 👇

NATALEE, NSABP B-42, PANKU-Breast01, TALENT, HERIZON-GEA-01, KEYNOTE-866 ve RASolute-302. Sağkalım faydası nerede gösterildi? Hangi çalışma primer sonlanımını karşılayamadı? Yeni verileri hasta grubu ve tedavi bağlamıyla birlikte değerlendirdik. #ESMO2026 https://t.co/gsMeDN50vu

Three new ADCs at ESMO 2026, three targets: HER2 (TQB2102, APEX-Breast01), EGFR x HER3 (iza-bren, PANKU-Breast01), nectin-4 (SHR-A2102, cervix). One payload: TOPO1 inhibitor. In cervix, the approved ADC is tisotumab, an MMAE payload, so a TOPO1 ADC after it is a real mechanism switch. In breast after T-DXd, a new target on the same payload is a different bet, and cross-resistance is the open question. The trial I want randomizes by payload sequence, not by target. #gyncsm #ESMO26 @myESMO

🚨 #ESMO26 moves fast your inbox should help you keep up, not add more noise. @OncoAlert The daily @OncoAlert Newsletter is LIVE from Madrid 🇪🇸 and delivers the most relevant congress data straight to your inbox every morning. 📌 Day 1 highlights 🎗️ NATALEE 6-year OS 🧬 PANKU-Breast01 + Lancet publication 🟠 KEYNOTE-866 & ENERGIZE two important negative MIBC trials 🟣 HERIZON-GEA-01 3-year OS 🎯 Why this matters: congress coverage is not about reading everything. It is about identifying the data that deserve attention, understanding what they mean, and moving quickly from headline to clinical context. That is what @OncoAlert does best: Less noise. More signal. Science that matters. 🤝 For colleagues, by colleagues. 📩 Register FREE: https://t.co/NFi1ia680V 👉 Subscribe: https://t.co/kHfE8oDWmE @DrChoueiri @PGrivasMDPhD @AndreaNecchi @TiansterZhang @hoperugo @stolaney1 @christine_lovly @CathyEngMD @BenWestphalen @nataliagandur #OncoAlert #ESMO26 #Oncology #CancerResearch #MedicalEducation

#ESMO26 | Impressive results with a next-generation bispecific ADC! Phase III PANKU-Breast01: EGFR×HER3-targeting iza-bren improved median PFS in HR+/HER2− metastatic breast cancer (8.2 vs 4.0 months; HR 0.41). However, grade ≥3 treatment-related AEs reached 85.3%. Key questions: Do ESR1, PIK3CA, or PTEN alterations influence response? What is the impact of prior ADC exposure? #ESMO26 #BreastCancer #ADC @myESMO @oncodaily @OncoAlert

🚨 Day 1 highlights from #ESMO26 are here! Subscribe for FREE 👉 https://t.co/Q2y6eL4mxY From NATALEE and PANKU-Breast01 to KEYNOTE-866, ENERGIZE & HERIZON-GEA-01 - stay updated with @OncoAlert, straight to your inbox every morning! 📩 https://t.co/ojhxebvmd6

#ESMO26 | PANKU-Breast01 Phase III: iza-bren, an EGFR×HER3 bispecific ADC, vs chemotherapy in previously treated HR+/HER2− advanced BC (N=383). ▪️ mPFS: 8.2 vs 4.0 months HR 0.41 (95% CI 0.33–0.53); P<0.0001 ▪️ ORR: 40.5% vs 20.2% ▪️ OS immature ▪️ Grade ≥3 TRAEs predominantly hematologic; ILD 1.1% (grade 1–2) Promising efficacy. Key question: where will it fit in ADC sequencing? 🔹 𝗕𝗠𝗦’𝘀 𝗼𝗻𝗴𝗼𝗶𝗻𝗴 𝗜𝗭𝗔𝗕𝗥𝗜𝗚𝗛𝗧-𝗕𝗿𝗲𝗮𝘀𝘁𝟬𝟭 𝘪𝘻𝘢-𝘣𝘳𝘦𝘯 𝘪𝘯 𝘢 𝘥𝘪𝘧𝘧𝘦𝘳𝘦𝘯𝘵 𝘱𝘰𝘱𝘶𝘭𝘢𝘵𝘪𝘰𝘯: 1𝘓 𝘢𝘥𝘷𝘢𝘯𝘤𝘦𝘥 𝘛𝘕𝘉𝘊 𝘰𝘳 𝘌𝘙-𝘭𝘰𝘸/𝘏𝘌𝘙2− 𝘉𝘊 𝘪𝘯𝘦𝘭𝘪𝘨𝘪𝘣𝘭𝘦 𝘧𝘰𝘳 𝘢𝘯𝘵𝘪–𝘗𝘋-(𝘓)1 𝘵𝘩𝘦𝘳𝘢𝘱𝘺. #Breastcancer #ADCs #PANKUBreast01

PANKU-Breast01 | #ESMO26 Iza-bren significantly improved PFS in pretreated HR+/HER2− advanced #BreastCancer vs physician’s choice chemotherapy (8.2 vs 4.0 months; HR 0.41). @OncoAlert #bcsm https://t.co/FS1TSa1cLo

PANKU-Breast01 at #ESMO26: izalontamab brengitecan, an EGFR×HER3 bispecific ADC, doubled PFS vs physician's-choice chemo in pretreated HR+/HER2- MBC (8.2 vs 4.0 mo, HR 0.41). A new target pairing after CDK4/6 - promising, though a Chinese-only population. #ESMOAmbassadors @myESMO https://t.co/s4PYcCD56O

📌 Proffered paper 1: Breast cancer, early and advanced stage ✨PANKU-Breast01: Randomized Phase III Study of Izalontamab Brengitecan in Previously Treated Unresectable Locally Advanced or Metastatic HR+/HER2- Breast Cancer Presented by ✨ Bo Lan 👉🏻In this pre-specified analysis, iza-bren demonstrated a statistically significant and clinically meaningful improvement in PFS vs TPC in previously treated HR+/HER2-BC, meeting the primary endpoint. 👉🏻Iza-bren demonstrated an improved confirmed ORR and more durable response than TPC. #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF

#ESMO2026 Panku-breast01 Izabren sig. improves PFS in met HR+HER2 post CDK4i #BreastCancer 👏New targets 🎈impressive ORR too ➡️broadly comparable to DB04 - here all HER2 But 🎈haem tox Still have the what next issue 🤷🏻‍♀️ Online publication in @TheLancetOncol #ESMOAmbassadors #bcsm @OncoAlert @myESMO

PANKU-Breast01 🇨🇳: dual EGFR and HER3 ADC Iza-Bren vs TPC in HR+/HER2- pre-treated MBC: 🔹 Median PFS improvement with Iza-bren: 8.2 vs 4 months (HR 0.41) 🔹 OS immature 🔸 More grade 3 AEs with Iza-bren #ESMO26 #ESMOAmbassadors @myESMO @PTarantinoMD @E_de_Azambuja https://t.co/ORpXqVnLMk

PANKU-Breast01 presented at #ESMO26 Iza-bren vs CT in HR+/HER2- after ET and 1 or 2 lines of CT ✅️ significantly improved PFS Mostly hematologic toxicity, 1% ILD events @OncoAlert https://t.co/Xwo7yVmiTM

Oral abstract #BreastCancer session at #ESMO26: results from PANKUbreast01 published in @TheLancet shoring efficacy of bispecific ADC #IzaBren in pretreated patients with HR+/HER2- advanced disease @OncoAlert @myESMO https://t.co/QJy9STIjLz

PANKU-Breast01 #ESMO26 Iza-bren (EGFRxHER3-ADC) significantly improved PFS vs chemotherapy in pretreated HR+/HER2− advanced breast cancer (8.2 vs 4.0 months; HR 0.41). ORR doubled (40.5% vs 20.2%), with manageable safety (ILD 1.1%). OS remains immature. https://t.co/EfZyLTGV02

🇨🇳 PANKU-Breast01: the HER3-EGFR bispecific TOPO1 ADC Iza-Bren improved PFS vs chemo in HR+/HER2- MBC (OS immature). High rate of hematologic toxicity, with ~50% G3+ anemia, neutropenia and thrombocytopenia, and most patients requiring dose reductions⚠️. #ESMO26 #ESMOAmbassadors https://t.co/f1zn2X0bpe

PANKU-Breast01 HR+ MBC, prior cdk 4/6i, 1-2 prior chemo Iza-bren vs TPC ~70% 1 prior chemo PFS 8.2 vs 4.0 mo, HR 0.41 p<0.0001 ORR 40.5% vs 20.2% DOR 6.9 mo vs 4.2 mo OS immature Most tox: heme tox, primary GCSF was not required @OncoAlert #ESMO26 https://t.co/zdUlK7U21Q

#PANKUBreast01 Ph III results for iza bren (bispecific EGFR/HER3 ADC) vs TPC chemo, in previously treated HR +/HER- MBC 🔹mPFS: 4.0 vs. 8.1 mo, HR 0.41 🔹 ORR: 20% vs 40% 🔹 DoR: 4.2 vs. 6.9 mo 🔹 ILD: only 1.1% & all grade 1/2 #ESMO26 #ESMOAmbassadors https://t.co/ikHLXiLHX1

#ESMO26 | PANKU-Breast01 In HR+/HER2− mBC, the EGFR/HER3 bispecific ADC (iza-bren): PFS: 8.18 vs 4.05 months (HR 0.41). Grade ≥3 TRAEs: 40.5% vs 20.2%. OS remains immature. An impressive PFS benefit. However, in an era when ADCs such as T-DXd and SG are already in use, superiority over chemotherapy alone is not enough. Another treatment option… The added value of bispecific targeting, particularly its efficacy after other TOP1-ADCs, remains uncertain. These are the key data needed to define its place in treatment sequencing.

🚨 ESMO 2026 | PANKU-Breast01 (LBA50) #esmo26 Impressive phase III results for izalontamab brengitecan (iza-bren), a bispecific EGFR/HER3 ADC, in previously treated MBC HR +ve Her2 -ve Iza-bren vs physician's choice chemotherapy: 🔹 Median PFS: 8.18 vs 4.01 months 🔹 HR 0.41 (95% CI 0.33–0.53; p<0.0001) 🔹 ORR: 40.5% vs 20.2% 🔹 Median DoR: 6.93 vs 4.21 months 🔹 ILD: 1.1% (all grade 1–2) 🔹 OS: Immature A remarkable 59% reduction in the hazard of progression or death, with manageable toxicity. Another ADC enters the increasingly crowded HR+/HER2− breast cancer landscape. @OncBrothers @myESMO @OncoAlert

Overall Day 1 message in bladder cancer: Not all perioperative IO strategies are equal. Adding PD-1/PD-L1 inhibitors to cisplatin-based chemotherapy has now failed in two large Phase 3 trials (KEYNOTE-866 and ENERGIZE), while EV + pembrolizumab-based approaches (and NIAGARA) have succeeded. Biomarker selection is increasingly important. @myESMO @OncoAlert @OpenMedicineHQ @tompowles1 @AndreaNecchi @Uromigos @urologysummit #ESMO26

🚨 Perioperative immunotherapy in MIBC at #ESMO2026. Three phase III trials, three different answers, and one uncomfortable lesson for those of us who report pCR. 🔬 📊 NIAGARA (durvalumab + GC, n=1,063): pCR 37.3%, EFS HR 0.68 (0.56–0.82), OS HR 0.75 (0.59–0.95) ✅ 
📊 KEYNOTE-866 (pembrolizumab + GC, n=907): pCR 44.4%, EFS HR 0.88 (0.71–1.10), OS HR 1.00 (0.76–1.27) ❌ 
📊 CA017-078 (nivolumab + GC, n=653): pCR 39.1%, EFS HR 0.94 (0.71–1.25), OS HR 0.88 (0.64–1.21), OS immature ❌ Cross-trial, not head to head. Populations, schedules, follow-up (34 to 55 months) and statistical design all differ, so the ranking is exploratory. But look at the direction. The trial with the highest pCR returned an OS hazard ratio of exactly 1.00. 🧠 Three points from the pathology side: 1️⃣ pCR is a response marker, not a surrogate. Comparable absolute pCR gains of roughly 9 to 10 points across all three, divergent survival. If pCR tracked cure, that pattern should not be possible. pCR remains elusive at least for standard chemotherapy plus IO. 2. And pCR itself is not standardised across trials. ypT0N0 depends on sampling protocol, block numbers, regression assessment and whether review is central or local. The NIAGARA figure quoted here comes from a reanalysis, which tells you the endpoint moved on re-review. A 9-point difference is not comfortably above that measurement noise. Also worth noting: NIAGARA and KEYNOTE-866 both gave adjuvant IO, CA017-078 did not. So adjuvant continuation alone does not explain the split either. We genuinely do not know why these diverged. 🎯 Which is the real message. We are comparing trials on an endpoint we produce, that is not validated, not standardised, and not stratified by biology. Fixing that is a pathology job, and it is overdue. We need that now more than ever with neoadjuvant systemic phase becoming SOC. @OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot #Uropathology #BladderCancer #blcsm #MIBC #pathtwitter Great summary below from Niklas Klümper.

🚨 Day 1 highlights from #ESMO26 are here! Subscribe for FREE 👉 https://t.co/Q2y6eL4mxY From NATALEE and PANKU-Breast01 to KEYNOTE-866, ENERGIZE & HERIZON-GEA-01 - stay updated with @OncoAlert, straight to your inbox every morning! 📩 https://t.co/ojhxebvmd6

#ESMO26 @AndreaNecchi presented ENERGIZE (CA017-078), comparing perioperative nivolumab + gemcitabine/cisplatin vs GC alone (N=653). 🔹 pCR: 39.1% vs 29.6%, but statistical threshold not met 🔹 EFS: HR 0.94; p=0.67 🔹 OS: HR 0.88 (descriptive) 🔹 Grade ≥3 AEs: 73% vs 56% 🧬 ctDNA clearance was strongly prognostic for EFS and OS, but neither baseline ctDNA status nor clearance identified patients who benefited more from nivolumab. @UroToday @myESMO

Bravo @AndreaNecchi on a superb presentation of ENERGIZE trial at @myESMO #ESMO26 ! 👏 Ph3, n=653 cis-eligible MIBC: neoadj GC + nivo → adj nivo vs GC alone. Median f/u 54.5 mo. 🔹 pCR 39.1% vs 29.6%: not dig
🔹 EFS HR 0.94: co-primaries not met
🔹 OS HR 0.88 👉Negative trial, but the ctDNA data are a key message: detectable ctDNA at baseline and after NAC strongly prognostic for worse EFS & OS. Selecting patients by ctDNA, rather than adding IO for all, is where the field is heading! Great to see this build on our Ph2 BLASST-1. Despite the negative result, it's very practice-informing. Proud to be a part of this effort! @CleClinicMD @caseccc @CleClinicUro @sonpavde @MattGalsky @MichvdHeijden @Uromigos @Annals_Oncology @tompowles1

#ESMO26 More perioperative evidence in cis eligible MIBC from CA017-078 Adding perioperative nivolumab to GC failed to improve EFS (HR 0.94) despite a numerical increase in pCR (39% vs 29.1%). Exploratoy data presented on ctDNA supports its prognostic value. @OncoAlert https://t.co/rTOuNwNBMp

Two periop cis gem based phase 3 trials, adding a PD-1 to neoadjuvant cis-gem in MIBC did not improve EFS. 📉 KEYNOTE-866 pembro: EFS HR 0.88, OS HR 1.00 📉 CA017-078 nivo: EFS HR 0.94, pCR 39.1% vs 29.6% missed sig 🔍 Both continued the PD-1 after cystectomy, 13 cycles of pembro and 9 of nivo ctDNA was prognostic in but did not enrich for who benefited #ESMO26 #BladderCancer #MIBC #GUonc

5 phase III perioperative MIBC trials, with differing results. EV-303, EV-304 and NIAGARA improved EFS/OS, while ENERGIZE and KEYNOTE-866 did not meet their EFS endpoints. Important differences in patient populations, regimens and trial design. Cross-trial comparisons require caution. #ESMO26 @OncoAlert

ENERGIZE: perioperative CisGem +/- Nivo in MIBC. No improvement in survival endpoints, just like KN-866. Food for thought… #ESMO26 https://t.co/WvI1UDVNMD

🎯 #ESMO26 ENERGIZE ph3 trial presenting by @AndreaNecchi other periop of IO therapy in MIBC! Cis-Gem + Nivo vs Cis-Gem! Other negative study of IO + cisplatin-based chemo!🧐 Reinforce the value of ADC + Pembro in this setting! @OncoAlert @myESMO @GuardConsortium @PGrivasMDPhD @apolo_andrea

Another negative Ph.III perioperative IO trial by @AndreaNecchi : CA017-078 evaluates Nivo + Gem/Cis -> surgery -> adjuvant Nivo vs Gem/Cis alone in MIBC. EFS HR 0.94 (95.74% CI 0.71-1.25), p=0.67. pCR 39.1% vs 29.6% (NS). OS HR 0.88. Important implications for perioperative IO strategies. #ESMO26 #BladderCancer @myESMO @OncoAlert

🚨⭐🟠 #ESMO26 | Abstract 4736O | ENERGIZE (CA017-078) Phase III trial of neoadjuvant chemotherapy ± nivolumab followed by adjuvant nivolumab in muscle-invasive bladder cancer (MIBC) 🎤 Presented by @AndreaNecchi 🇮🇹 @OncoAlert @urologysummit 🔬 Can perioperative nivolumab improve outcomes in patients with cisplatin-eligible MIBC? 📊 STUDY DESIGN Phase III randomized trial | N=653 🔹 Nivolumab + gemcitabine/cisplatin → radical cystectomy → adjuvant nivolumab (n=325) 🔹 Gemcitabine/cisplatin → radical cystectomy → observation (n=328) 📊 KEY RESULTS ❌ Event-free survival (co-primary endpoint) • Median EFS: NR vs 67.6 months • HR 0.94 (95% CI 0.72–1.24) • p=0.6697 ➡️ No statistically significant improvement. 📈 Pathological complete response (co-primary endpoint) • pCR: 39.1% vs 29.6% • Absolute difference: +9.5 percentage points ❌ Did not meet the prespecified multiplicity-adjusted significance threshold. 🔬 Combined pathological response (≤ypT1N0) • 51.7% vs 41.8% 🧬 ctDNA EXPLORATORY ANALYSIS ✅ Neoadjuvant ctDNA clearance: • 81.3% vs 71.7% 📌 Pretreatment ctDNA positivity was associated with shorter EFS and OS. However, no clear differential treatment benefit was observed according to baseline ctDNA status. 📊 Overall survival • OS data remain immature. • No established survival advantage. ⚠️ Safety was consistent with the known profiles of the individual agents. 🔬 CONCLUSION Adding perioperative nivolumab to neoadjuvant gemcitabine/cisplatin did not significantly improve the co-primary endpoints of pCR or EFS in patients with MIBC. ⭐ MY POINT OF VIEW | CLINICAL PEARL Improving pathological response does not necessarily translate into better long-term outcomes. ENERGIZE reinforces an essential principle in perioperative oncology: pCR signals must be interpreted alongside EFS, OS, toxicity and statistical robustness. 🧬 ctDNA is emerging as a powerful prognostic biomarker, but its ability to guide treatment intensification or de-escalation still requires prospective validation. 💡 The future of perioperative MIBC treatment is not simply adding more immunotherapy. It is identifying who truly benefits—and who can safely avoid unnecessary treatment. 🌍 GU Oncology Community @gbanna74 @ravikanesvaran @tompowles1 @PGrivasMDPhD @apolo_andrea @sonpavde @montypal @TiansterZhang @DrYukselUrun @drenriquegrande @cdanicas @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #MIBC #GUOncology #ClinicalTrials #OncoAlert

@AndreaNecchi with phase 3 #ENERGIZE trial results — cis gem nivo vs cis gem in muscle invasive #bladdercancer. 10% path CR rate diff but no diff on EFS or OS. ctDNA (+) at baseline has poor prognosis. @oncoalert #ESMO26 @myESMO https://t.co/HTP7Fwmx6p

🚨 Another negative phase III trial at #ESMO26! CA017-078: Perioperative nivolumab + gemcitabine/cisplatin failed to significantly improve outcomes in MIBC. 🔹 pCR: 39.1% vs 29.6% (not statistically significant) 🔹 EFS: HR 0.94 (95% CI 0.72–1.24); P=0.6697 #BladderCancer https://t.co/ENr8C08YbS

#ESMO26 | Final results from CheckMate 274? No—CheckMate 7G8 (CA017-078) in MIBC. Nivolumab + GC improved pCR (39.1% vs 29.6%), but neither pCR nor EFS met statistical significance. @SCUColombia @achoHematoYOnco @myESMO @ASCO @OncoAlert @oncodaily https://t.co/xLhIbQL9Jd

KEYNOTE-866: Negative for EFS. ENERGIZE: Negative for EFS. → What made the difference between these trials and NIAGARA? #ESMO26 https://t.co/vqu0TprzZx

#ESMO26 Day 1 has arrived! Follow along with @OncoAlert for full coverage! Highlights from the GU Renal & Urothelial Proffered Paper Session today: 🔴 Ph 3 KEYNOTE-866 (GC +/- perioperative pembro in MIBC) 🔴 Ph 3 ENERGIZE (GC +/- perioperative nivo in MIBC) 🔴 Ph 1 TROPHYU-01 Cohort 7 (SG + EV + Zim in 1L La/mUC) 🔴 ctDNA analyses from Ph 3 KEYNOTE-B15 (EV+P vs GC in cis-eligible MIBC) Key❓: Why were KN-866 and ENERGIZE negative while NIAGARA was positive? @scocmem @nataliagandur @DrKarineTawagi @niklas_kluemper @OncoAlert

#ESMO2026 🚨 Three phase III trials with perioperative chemoimmunotherapy. Different outcomes in MIBC. NIAGARA: durvalumab + GC → EFS HR 0.68, OS HR 0.75 ✅ KEYNOTE-866: pembrolizumab + GC → EFS HR 0.88, OS HR 1.00 CA017-078: nivolumab + GC → EFS HR 0.94 Interestingly, all three showed numerically higher pCR rates, but only NIAGARA demonstrated statistically significant survival benefits in the reported analyses. Why? Differences in trial populations, treatment schedules, statistical design—or tumor biology? These are cross-trial observations, not head-to-head comparisons. We should resist attributing the differences simply to PD-1 versus PD-L1 inhibition. The key challenge: identifying which MIBC patients truly benefit from adding immunotherapy to chemotherapy. We urgently need predictive biomarkers and molecularly informed perioperative treatment selection. 🔬 @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot @Markuseckstein3

STATISTICALLY POSITIVE. CLINICALLY THIN. KEYNOTE-B49: pembrolizumab + chemo delivered just +0.7 months median PFS in PD-L1 CPS≥1 HR+/HER2− advanced breast cancer with no OS benefit. Significance ≠ meaningful benefit. @hoperugo #ESMO26 https://t.co/KrBy46HOX1

#ESMO26 @myESMO #ESMOAmbassords new data from Keynote-b49 👇🏼 https://t.co/IVkZskoV3K

Huge congrats to @hoperugo @cityofhope on her presentation at #ESMO26 of the final analysis of #KNB49 & simultaneous publication in @Annals_Oncology! @OncoAlert https://t.co/KX3Sk3mh7T

KEYNOTE-B49 at #ESMO26 In pretreated HR+/HER2− metastatic breast cancer, pembrolizumab + chemotherapy improved PFS (HR 0.74; 6.7 vs 6.0 months), with 99% previously exposed to CDK4/6 inhibitors. https://t.co/6PnmjT6RMs #BreastCancer @OncoAlert #BCSM @myESMO https://t.co/P34WnjwnEE

#ESMO26 #ESMOAmbassadors My take on KEYNOTE B49: https://t.co/u6abclEeDO

🔥 KEYNOTE-B49 meets its primary endpoint, but benefit seems limited to few patients 👉 ICIs benefit selected ER+/HER2− BC pts (CPS≥10, ER-low) 👉 Are ADCs better ICI partners than CT? 👉 What about PD-1/VEGF bispecifics? ➡️ Better biomarkers urgently needed! #ESMO26 https://t.co/xtA0X9K0CZ

Another reminder that immunotherapy is not a universal solution. KEYNOTE-B49 highlights the need for better patient selection. @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 https://t.co/J8P0GfjTfZ

After so much effort to bring immunotherapy into HR+/HER2− mBC, KEYNOTE-B49 raises a hard question: is this worth it? A 0.7-month median PFS gain and no demonstrated OS benefit. We need more meaningful returns for our patients. #ESMO26 @myESMO @Larvol @OncoAlert https://t.co/cPcmj5y5cu

KEYNOTE-B49 presented by @hoperugo at #ESMO26 Addition of pembro to CT in PDL1+ HR+HER2- mBC with no previous CT for metastatic BC ✅️primary PFS endpoint reached (curves opening at tails) ✅️higher magnitude of PFS benefit in CPS >=10 ❌️no sign OS difference @OncoAlert https://t.co/waxv3MV2T5

Keynote B49 - pembrolizumab does not work much in this Hr positive Her2 negative MBC population( endocrine resistant ) @myESMO @dr_yakupergun @OncoAlert #esmo26 https://t.co/JG3iBEFWSU

📌 Proffered paper 2: Breast cancer, early and advanced stage Results from KEYNOTE-B49: A phase 3, randomized, double-blind study of pembro vs placebo plus chemotherapy in pts with HR+/HER2- advanced breast cancer ✨@hoperugo #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/Q1VhNeWx0Z

KEYNOTE-B49 #ESMO26 Pembrolizumab + chemotherapy improved PFS in PD-L1+ HR+/HER2− advanced breast cancer (HR 0.74), with greater benefit in CPS ≥10 (HR 0.59). No significant OS or overall ORR benefit. Immune-mediated AEs were more frequent. https://t.co/3nbuYmGuW5

今回の注目試験の一つ、PD-L1(CPS>1) HR+/HER2ーの化学療法へのペムブロ上乗せをみたKEYNOTE-B49。 PFSは有意に延長(HR 0.74)。ただ、6.7M vs 6.0と臨床的に有意とは言い難い。 CPS>10では良さそうな傾向。OSは延長なし。Practice changningとはいかないか... Ann Oncolに同時掲載。 #ESMO26 https://t.co/DYwLbq4CMO

Keynote B49 -chemo + pembro vs chemo in HR+ PD-L1 +: better PFS but only 0.7 mos and no OS benefit - no ADC comparator #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO @Annals_Oncology https://t.co/4yvA69gS8c

KN-B49 @hoperugo PDL1+ HR+ MBC after ET tx w/chemo +/-Pembro Chemo: cape, doxil, taxanes Pembro improved mPFS 6 to 6.7 mos; no OS gain Complicated for practice w/ modest gain, ADCs in a competing space, and the pt burden of adding Pembro to oral cape. #ESMO26 @OncoAlert https://t.co/durudyjrCs

KNB49 HR+ adv #bcsm with PDL+, chemo +/- pembro once chemo appropriate Only 19.4% of pts eligible (majority weren't PDL1+) ~79% of + were CPS 1-9 PFS improved 6 to 6.7 mo, but tail of curve much better at 24 mo 4.3 vs. 14% remaining on PFS CPS of 19 4.4 vs. 7.5 mos #ESMO26 https://t.co/pwtswREUTg

Oral abstract #BreastCancer session at #ESMO26: super @hoperugo presenting results from KeynoteB49 trial…more translational research is needed to improve our understanding on how to optimize #immunotherapy use in luminal-like disease @OncoAlert @myESMO #pembrolizumab https://t.co/KMFql1Fmzp

#ESMO26 | KEYNOTE-B49 In patients with PD-L1 CPS ≥1, HR+/HER2− mBC previously treated with ET, pembro + chemo was compared with chemo - PFS: 6.7 vs 6.0 mo (HR 0.74) - OS: 21.0 vs 22.2 mo (HR 1.04) - CPS ≥10: PFS HR 0.59 I’m curious to see the subgroup analyses presented at ESMO. However, in the ADC era, this modest PFS benefit without an OS advantage has little clinical relevance to me. Evaluating immunotherapy in combination with ADCs or after ADC treatment may be more rational in today's treatment landscape.

FourLight-1 #ESMO26 In HR+/HER2− advanced #BreastCancer after CDK4/6i progression,atirmociclib + fulvestrant improved median PFS to 9.4 vs 6.6 months (HR 0.60; p=0.0007) Promising results,but phase 3 validation is needed to establish its role in clinical practice. @OncoAlert https://t.co/a1rxIUxRzG

🔥 FOURLIGHT-1 demonstrates atirmociclib efficacy post-CDK4/6i ⚠️ Phase II trial: not practice-changing yet 👉 These results reinforce expectations that atirmociclib may outperform other CDK4/6i ➡️ FOURLIGHT-3 results eagerly awaited Congrats to my friend @antgiorda #ESMO26 https://t.co/IBGIoA05Rc

Can selective CDK4 inhibition overcome resistance to CDK4/6 inhibitors? Interesting data presented at #ESMO26! In the randomized Phase II FOURLIGHT-1 trial, atirmociclib + fulvestrant improved median PFS compared with investigator's choice after prior CDK4/6 inhibitor therapy: 9.4 vs 6.6 months | HR 0.60 Selective CDK4 inhibition may offer a new strategy after CDK4/6 inhibitor progression, potentially with improved tolerability. But the key question remains: Can selective CDK4 inhibition outperform current CDK4/6 inhibitors in the first-line setting? FOURLIGHT-3 may provide the answer. #ESMO26 #BreastCancer #PrecisionOncology #CDK4 @myESMO @oncodaily @OncoAlert @OncBrothers @PTarantinoMD

Am I the only one at #ESMO26 who thinks FOURLIGHT-1 lacks an appropriate comparator? Why not use everolimus plus endocrine therapy (investigator’s choice) as the control arm, as in evERA? #ESMOAmbassadors @myESMO https://t.co/pAOS02wRcT

After CDK4/6i in HR+ MBC, the control arm is the story at #ESMO2026. FINER: fulvestrant alone, median PFS 1.9 mo. Ipatasertib + fulvestrant 5.4 mo, HR 0.68. In AKT pathway-altered tumors, HR 0.55.
FOURLIGHT-1: atirmociclib, a CDK4-selective inhibitor, 9.4 vs 6.6 mo with investigator's choice, HR 0.60. 85 to 92% randomized within 3 months of their last CDK4/6i. Fulvestrant alone after a CDK4/6i is close to no treatment. FINER helped even without selection, but with toxicity FOURLIGHT-1 tests whether keeping CDK4 pressure on, more selectively, beats switching. #bcsm #ESMO26 @myESMO

Great to see my longtime friend @antgiorda present FOURLIGHT-1 at #ESMO26: atirmociclib + fulvestrant improved PFS vs investigator's choice after prior CDK4/6 (9.4 vs 6.6 mo, HR 0.60). Encouraging data after CDK4/6. #ESMOAmbassadors @myESMO https://t.co/beBzI9zSQZ

Proffered paper BC session 2 at #ESMO26: Great to see EVE + ET as comparator arm in post-CDK4/6i RCT The ph2 FOURLIGHT-01 trial: Atirmociclib (selective CDK4i) + fulvestrant shows a clinically meaningful PFS of 9,4 months vs 6,6 (fulve / exe + eve) #ESMOAmbassadors @myESMO https://t.co/f2v5Eb5qzv

🔹CDK4 selective inh Atirmociclib + fulvestrant improved mPFS vs investigator’s choice post-CDK4/6i in the FourLight-1 ph2 trial 🔹Neutropenia the most frequent AE & 1 related pneumontis death 🔹Next step: the FourLight-3 ph3 study in the 1L vs CDK4/6i #ESMO26 #ESMOAmbassadors https://t.co/M7QkbXoYmZ

📌 Proffered paper 2: Breast cancer, early and advanced stage Efficacy and safety of atirmociclib + fulvestrant in pts with HR+/HER2- advanced/mBC who progressed on prior CDK4/6i in a randomized phase 2 study (FOURLIGHT-1) ✨ @antgiorda #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/PfchBejByO

FourLight-1 presented by @antgiorda at #ESMO26 Atirmociclib + fulvestrant improved median PFS vs investigator’s choice after CDK4/6i progression in HR+/HER2− metastatic breast cancer (9.4 vs 6.6 months; HR 0.60; p=0.0007) @DFCI_BreastOnc @OncoAlert https://t.co/Izo75JxXQx

#FOURLIGHT1 CDK4 atirmociclib Fulv + atirmo vs TPC (fulvestrant or exe/evero) post ET+ CDK4/6 in ER+ #bcsm PFS improved 6.6 to 9.4 mos, HR 0.60 #ESMO26 #ESMOAmbassadors @OncoAlert **1st line trial and curative trials coming!*** https://t.co/fCu7aFNbUq

At #ESMO26 Proffered Paper 2️⃣ on #breastcancer @antgiorda presents FOURLIGHT-1 Atirmociclib (CDK4i) + fulvestrant in HR+ aBC after PD to CDK4/6i ⬆️ PFS (delta of 3 months) Ongoing ph3 trial of atirmociclib in 1 line @OncoAlert https://t.co/PJlzwUgyDS

FOURLIGHT-1 #ESMO26 @antgiorda Atirmociclib + fulvestrant significantly improved PFS vs investigator’s choice in HR+/HER2− metastatic breast cancer after CDK4/6i (9.4 vs 6.6 months; HR 0.60). CBR was higher (61.9% vs 46.0%), with manageable safety, although grade ≥3 AEs were more frequent.

FourLight shows 1st CDK4i Atirmociclib after CDK4/6i shows significant improvement in mPFS 9.4 vs 6.6 mos HR=0.60 notable AE neutropenia #ESMO26 @OncoAlert https://t.co/1z1a5CkDFq

#ESMO26 | FOURLIGHT-1 In HR+/HER2− mBC after CDK4/6i, the selective CDK4 inhibitor atirmociclib + fulvestrant improved PFS. PFS: 9.4 vs 6.6 mo (HR 0.60) 12-month PFS: 44.8% vs 22.5% Selective CDK4 inhibition after CDK4/6 inhibition! The sustained separation of the PFS curves is noteworthy.

@antgiorda beautifully presents our data from Fourlight 1 with the CDK4i atirmociclib/fulv vs fulv or eve/exe as 2nd line Rx for HR+ MBC. At 13.7 mo med FU, n=263, 38%esr1m, 40% PIKm, PFS 9.4 v 6.6mo HR 0.6 p0.007. Beautiful data. Await Fourlight 3 1st line study! @OncoAlert

🧬 After progression on a CDK4/6 inhibitor, is it time to rethink whether the class can still work? @OncoAlert At #ESMO26, randomized phase II FOURLIGHT-1 evaluated atirmociclib + fulvestrant versus investigator’s choice in HR+/HER2– advanced #BreastCancer after prior CDK4/6 inhibition. 📊 n=263 ➡️ Median PFS: 9.4 vs 6.6 months HR 0.60 (0.440–0.825) ➡️ ORR: 19.3% vs 11.3% ➡️ CBR: 61.9% vs 46.0% ⚠️ Neutropenia was the most common TRAE, but treatment discontinuation due to TRAEs was only 4.0% 🎯 Why this matters: resistance to one CDK4/6 inhibitor may not mean the pathway is exhausted. For me, the key signal here is that a next-generation CDKi can recapture meaningful disease control after prior CDK4/6 exposure. The next questions are the ones that will define the field: 🔹 who remains CDK-dependent? 🔹 which resistance mechanisms matter most? 🔹 and can biomarkers help us identify who should receive another CDK strategy versus switching pathway entirely? Excellent work from @antgiorda and the FOURLIGHT-1 investigators. Pinging @matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @hoperugo @stolaney1 @BianchiniGP @kevinpunie @GaiaGriguolo #OncoAlert #ESMO26 #BreastCancer #CDK46 #EndocrineTherapy #PrecisionOncology

🌟Context: EV + pembro already moved the bar perioperatively. 🧵2/2 🔑KEYNOTE-905/EV-303 (cisplatin-ineligible, vs surgery): EFS HR 0.40, pCR 57% vs 9% 🔑KEYNOTE-B15/EV-304 (cisplatin-eligible, vs cis-gem): EFS HR 0.53, OS HR 0.65 👉VOLGA adds a chemo-free durva + EV option to that landscape. 🔗 https://t.co/TMEcrvUZOM @LauraBukavinaMD @UroOnc @urotoday @UrologyTimes @myESMO @DrJJZhang @AmandaNizamMD @jgong15 @UCLAHealthJCCC @Uro_Oncologist

EV-303: EFS HR 0.40, OS HR 0.50 with 9 EV cycles. VOLGA gave 3, all neoadjuvant. future trials hopefully begin to ask what to do for component of parts adjuvant e.g. ctDNA neg no adjuvant unless converting to positive, ctDNA positive or lack of pCR switching ADC or MOA in the adjuvant setting.

Important data by Dr. Bedke & @AndreaNecchi in localized MIBC: periop addition of anti-PD1 not better vs neoadjuvant Gem/Cis alone; discordant with NIAGARA data. Periop EV/ICI combo has shown EFS/OS benefit from EV303/304 & VOLGA trials @myESMO #ESMOAmbassadors #ESMO26 @OncoAlert https://t.co/ypUFzGbu4B

💫#VOLGA: Durva + EV in cis-ineligible, like #EV303 but NO adjuvant EV here ⬆️ 2-year EFS (HR 0.51), OS (HR 0.58) & pCR (45% vs 10%) Triplet arm OS not significant & ⬆️ tox Less robust #s then EVP but how much benefit does adjuvant EV add? Can we use ctDNA/pCR to ⬇️? #ESMO26 https://t.co/UruMRqJPnI

VOLGA: perioperative EV + Durvalumab increases pCR, EFS and OS compared with cystectomy alone. A new standard option for these patients, in a setting that is becoming really crowded (NIAGARA, KN-905, KN-B15). #ESMO26 https://t.co/LdFwVrOXWH

With VOLGA results coming at #ESMO26, a summary of contemporary phase III perioperative trials in muscle-invasive bladder cancer. ⚠️ Different populations and designs—avoid cross-trial comparisons. VOLGA and EV-303 importantly include surgery-alone control arms without neoadjuvant therapy. 🔑 The next challenge: identifying who truly needs adjuvant ADC therapy—and who can safely avoid it. #BladderCancer #GUOnc @OncoAlert @BladderCancerUS

Circulating LBA — confirm at PS I (Powles). What is solid across multiple posts: EFS HR ~0.51, OS HR ~0.58. Absolute 2-yr rates differ by source; treat as unverified until slides. Open question after EC EV + pembrolizumab (EV-304/KN-905): how does neoadjuvant-only EV + peri-op durvalumab sit next to peri-op EV + pembro as today’s SoC?

💔 EV has a new partner! PEMBRO: “Another checkpoint inhibitor?!” 😳 EV: “We have survival data TOO!” ❤️ 🔥 VOLGA | ESMO 2026 EFS HR 0.51 | OS HR 0.58 But PEMBRO isn't out of the picture! KEYNOTE-905: EFS HR 0.40 | OS HR 0.50 Two promising perioperative partnerships in cisplatin-ineligible MIBC. ⚠️ Different trials. No head-to-head comparison. @myESMO @OncoAlert #MVOnco #ESMO2026 #BladderCancer

#ESMO26 | VOLGA | Presidential Symposium-1 In cisplatin-ineligible/refusing MIBC, neoadjuvant EV + perioperative durvalumab significantly improved EFS and OS vs the control arm. EFS: HR 0.55 (24-month: 78% vs 69%) OS: HR 0.58 (24-month: 83% vs 75%) pCR: 45% vs 10% Impressive results! Unlike KEYNOTE-905/EV-303, EV was administered only in the neoadjuvant setting, with no adjuvant EV. I’m looking forward to the discussion during the session.

🔬 Great summary by @niklas_kluemper on KEYNOTE-905/EV-303 at #ESMO2026. Let me add the pathology angle, because his key question is ours to answer. The ad hoc analysis, 255 concurrently randomised, cisplatin-ineligible: 📊 2-yr EFS 41% / 56% / 76% (cystectomy / pembro / EV+P)
🔬 pCR 10% / 25% / 59%
📉 EFS HR 0.71 (0.47–1.07) for pembro, 0.40 (0.25–0.65) for EV+P
⚠️ Grade ≥3 TEAEs 42% / 70% / 69% Two things I keep coming back to 🧠 1️⃣ The toxicity numbers look reassuring and are not. 70 vs 69% grade ≥3 says EV adds no extra severe events, but a single rate collapses two very different profiles. Neuropathy, skin and metabolic toxicity in a curative-intent setting are not interchangeable with immune-related events, and they persist in survivors. Equal rates, unequal consequences. 2️⃣ 41% of patients on EV+P still have residual disease. We will not find them just with a IHC cutoff. Membranous Nectin-4, read on the membrane only, together with histological subtype and divergent squamous differentiation, is the most informative combination we already have and routinely leave unmeasured. And a pathology point that follows directly: once pCR carries this much weight, ypT0N0 at cystectomy becomes a high-stakes diagnosis. Thus, Sampling protocols and regression assessment need to be standardised and centrally reviewed, not left to local practice. 🎯 Also worth stating plainly: this is an ad hoc comparison, not a powered head-to-head. Pembro alone did not separate from surgery here (CI crosses 1). Interpret the three-arm ranking accordingly. Looking forward to Sunday's symposium. 🎤 ESMO 2026 | KEYNOTE-905/EV-303 | Abstract 4733O @niklas_kluemper @OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot #Uropathology #BladderCancer #blcsm #pathtwitter

#ESMO26 How much does each drug contribute to perioperative EV + pembrolizumab in MIBC? 🚨A 3-arm analysis of KEYNOTE-905/EV-303 (N=255). EV+P vs P alone vs surgery: 🔹 3-year EFS: 69.5% vs 49.6% vs 37.4% 🔹 pCR: 58.8% vs 25.3% vs 10.3% 🔹 Pathologic downstaging: 65.9% vs 33.7% vs 14.9% 🔹 EFS HR vs surgery: 0.40 with EV+P; 0.71 with P alone 📌The efficacy gradient suggests both EV and pembrolizumab contribute to the combination's activity, with substantially greater benefit from EV+P. 📌Important caveat: descriptive, ad hoc analysis without formal statistical testing. @UroToday @myESMO

KEYNOTE-905: pembro alone raises a question worth testing. Who might safely need less? @myESMO @FAndreMD @curijoey @DrChoueiri @OncoAlert @OpenMedicineHQ #ESMO26 @Uromigos https://t.co/Qplp3Osdrc

Perioperative EV + Pembro momentum by #DrAndersUllen in KEYNOTE-905 Ph.III ad hoc analysis of cis-ineligible MIBC. 2-yr EFS: 75.8% EV/Pembro vs 55.8% Pembro vs 41.0% surgery alone. EFS HR 0.40 vs 0.71 (each vs control). pCR 58.8% vs 25.3% vs 10.3%. #ESMO26 #BladderCancer @myESMO @OncoAlert

🚨⭐🟠 #ESMO26 | Abstract 4733O | KEYNOTE-905 / EV-303 Perioperative Pembrolizumab or Enfortumab Vedotin + Pembrolizumab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer: Ad Hoc Analysis 🎤 Presented by Anders Ullén 🇸🇪 @OncoAlert 🔬 What is the contribution of each agent to the benefit of perioperative EV + pembrolizumab? 📊 STUDY DESIGN Exploratory 3-arm analysis | N=255 Patients with #MIBC ineligible for or declining cisplatin, concurrently randomized to: 🟢 EV + pembrolizumab (n=85) 🔵 Pembrolizumab alone (n=83) 🔴 Radical cystectomy + PLND alone (n=87) 📊 KEY RESULTS ✅ OVERALL SURVIVAL 🔹 EV + pembro vs control: HR 0.48 (95% CI 0.29–0.80) 🔹 Pembro vs control: HR 0.76 (95% CI 0.48–1.20) 📈 Median OS: • EV + pembro: NR • Pembro: 51.0 months • Control: 41.7 months ✅ PATHOLOGICAL COMPLETE RESPONSE 🟢 EV + pembro: 58.8% 🔵 Pembro: 25.3% 🔴 Control: 10.3% Absolute differences vs control: • EV + pembro: +48.6 percentage points • Pembro: +15.7 percentage points 📌 EFS and OS favored perioperative EV + pembro versus surgery alone, while pembrolizumab monotherapy showed numerically favorable outcomes. ⚠️ SAFETY Grade ≥3 AEs: • Neoadjuvant: 44.0% vs 20.7% (EV + pembro vs pembro) • Adjuvant: 60.0% vs 44.9% 🔬 INTERPRETATION The efficacy pattern supports a potential contribution of both EV and pembrolizumab. However, this was an ad hoc exploratory analysis, and comparisons should not be interpreted as confirmatory evidence of the independent contribution of each drug. ⭐ MY POINT OF VIEW | CLINICAL PEARL The question is evolving from whether perioperative EV + pembrolizumab works to understanding why the combination works—and which patients truly need both agents. The striking pCR difference and favorable OS signal reinforce the biological rationale for combining an ADC with immune checkpoint inhibition. 💡 But treatment intensification must always be balanced against toxicity, patient fitness and long-term benefit. 📌 EV + pembrolizumab is an established perioperative option for cisplatin-ineligible MIBC based on the parent KEYNOTE-905 trial. These exploratory findings add insight rather than establish a new treatment indication. 🌍 GU Oncology Community @gbanna74 @ravikanesvaran @urologysummit @tompowles1 @brian_rini @montypal @crisbergerot @DrDanielHeng @apolo_andrea @DrChoueiri @PGrivasMDPhD @TiansterZhang @HHammersMD @neerajaiims @amerseburger @sonpavde @drenriquegrande @scserendipity1 @Silke_Gillessen @EfstathiouEleni @BraunMDPhD @cdanicas @AOmlin @declangmurphy @salvolarosa @RenuEapen @seanmcbride @DrJaVallejo @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #MIBC #GUOncology #ADC #ClinicalTrials

🎯 #ESMO26 EV 303 study update! Perioperative pembro was associated with numerically better EFS and OS compared with RC! 💯@OncoAlert @myESMO @tompowles1 @PGrivasMDPhD @urotoday @GuardConsortium https://t.co/cP3d2BKht4

KEYNOTE-905 ad hoc analysis: EV + pembrolizumab vs pembrolizumab alone suggests that EV plays a key role in the neoadjuvant setting. But is adjuvant EV really necessary? Hopefully, VOLGA will provide some clues tomorrow! #ESMO26 https://t.co/dIXA5s9keB

DASL-HiCaP at #ESMO26, presented by @Niazi_Dr7: darolutamide + RT + 2 yrs ADT vs placebo in very high-risk prostate cancer (n=1,106) ▪️ MFS HR 0.42, 4-yr MFS 95% vs 88% ▪️ PSA-PFS HR 0.47 ▪️ Time to CRPC HR 0.22 ▪️ OS immature (HR 0.88) #ProstateCancer https://t.co/pfDHyuM2qW

@niazi_Dr7 with #DASL-HICAP trial ADT/XRT +/- darolutamide in high risk #prostatecancer. Darolutamide improves distant metastasis free survival. Similar AE profile. Highly powered trial. @ANZUPtrials @oncoalert @myESMO #ESMO26 https://t.co/5XfILDi89w

🚨📣📣 #ESMO26 presidential: @niazi_Dr7 Adding darolutamide to ADT + RT dramatically ⬇️ risk of metastasis or death in high-risk localized prostate cancer. Phase 3 DASL-HiCaP = 58% ⬇️ in MFS (HR 0.42) + early OS signal (HR 0.88). #ProstateCancer #RadOnc #pcsm @ChrisSweens1 https://t.co/7JuxQ3qSr9

DASL-HiCaP: ADT + RT +/- Darolutamide in very high risk localized prostate cancer or biochemically persistent/recurrent disease. Improvement in MFS. New evidence that ARPIs have a role in localized disease. Patient selection will be key. #ESMO26 https://t.co/dWHDhRzlvT

Compelling presentation by Tamim Niazi! DASL-HiCaP: adding darolutamide to ADT + RT improved MFS in very high-risk nonmetastatic prostate cancer (HR 0.42; 4-year MFS 95% vs 88%). Important phase III evidence for intensification! #ESMO26 @oncoalert @myESMO https://t.co/ALgNRFY3ka

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

Seven more men in a hundred stay metastasis-free at 4 years — if circulating DASL-HiCaP rates hold. Very high-risk localised prostate cancer: darolutamide + ADT + RT vs placebo + ADT + RT (n=1,106). 4-yr MFS 95% vs 88% (HR 0.42, 95% CI 0.27–0.66); OS not clear at interim. Absolute Δ +7 pp · NNT ≈14. Confirm at PS I (Niazi). #ESMO26 #LBA4 @zklaassen_md @jryckman3 @niazi_Dr7

⚡️LBA4⚡️ DASL-HiCaP (ANZUP1801) Ph 3 RCT #ESMO26 Daro + ADT and definitive/salvage locoregional RT for very HR PCa @urotoday 🚨n=1,106; mFU 3.8 yrs; 85% definitive RT 🚨Primary EP MFS by CI: ⏫ for Daro vs PBO - 4-year MFS-CI 95% vs 88% - HR 0.42 (95% CI 0.27 to 0.66)

Improved MFS w/ darolutamide in DASL-HiCaP! 📌 1,106 very high-risk prostate cancer pts, incl persistent/rising PSA after RP. Randomised to darolutamide vs placebo w/ ADT + RT. 📌 Median age 71; GS 9-10 73%; CT N+ 29%; prior RP 15%. 📌 4y MFS on conventional imaging: 95% vs 88%, HR 0.42 (95% CI 0.27-0.66). No clear OS benefit yet. 📌 All prescribed prostate/bed AND pelvic nodal RT, w/ 96 wk ADT. 📌 N+ = CT/MRI >10 mm short axis or path confirmation (PSMA PET alone insufficient if ≤10 mm). Side note: RT dose/fx and PSMA staging use aren't reported in the abstract. #radonc #ESMO26 #PCSM

Arriving at #ESMO26 tomorrow just in time for what promises to be one of the most exciting sessions: Presidential Session #1. #INTerpath-001 presented by @ProfGLongMIA, #VOLGA by @tompowles1, #DeLLphi-305 by @sands_jacob & #DASLHiCaP by @niazi_Dr7. A terrific slate of discussants as well, incl @StephenVLiu (one of the most talented orators in our field, IMHO), @MichvdHeijden, @Silke_Gillessen & more. Hats off to @YJanjigianMD, @FAndreMD, @Prof_Nadia_H & #DrJamesLarkin for assembling a powerhouse program! @OncoAlert

🚨 #ESMO26 GU Oncology — the studies I would keep closest on the radar @OncoAlert What stands out from the @OncoAlert GU selection is how clearly the field is moving toward perioperative intensification, biomarker-driven treatment, smarter sequencing, and new mechanisms of action. 🟠 #BladderCancer VOLGA · KEYNOTE-B15 · ENERGIZE · KEYNOTE-866 🔵 #ProstateCancer DASL-HiCaP · CAPItello-281 · PROTEUS 🟢 #KidneyCancer LITESPARK-011 · LITESPARK-012 · ivonescimab · PE-PE · SWOG S2200 · XmAb819 🎯 Why this matters: these are not just isolated trial readouts. Together, they are redefining where we intensify, where we de-escalate, how we select patients, and how earlier disease settings are becoming increasingly systemic and biology-driven. For me, the most important question across all three tumors is the same: Who actually needs more treatment — and who can safely receive less? That is where GU oncology is heading. Proud to be part of this @OncoAlert faculty following the data closely at #ESMO26. @DrChoueiri @tompowles1 @neerajaiims @PGrivasMDPhD @TiansterZhang @AndreaNecchi @DrRanaMcKay @DrYukselUrun @crisbergerot @nataliagandur #OncoAlert #GUOncology #PrecisionOncology #CancerResearch

✈️ En route to Madrid for #ESMO26, landing just in time for the data to start Friday morning. Most excited for: VOLGA LBA2 in bladder cancer, INTerpath-001's first phase 3 neoantigen win, LITESPARK-011 final in kidney cancer, and DASL-HiCaP in prostate. What a week ahead 🔬 #GUonc

#TALENT at #ESMO26 🇪🇸 : neoadjuvant T-DXd alone, T-DXd + anastrozole, or T-DXd followed by TC showed high response rates but pCR <10% across all arms in HR+/HER2-low early #BreastCancer Better biomarkers are needed to guide patient selection. @OncoAlert https://t.co/fLXRulAGXD

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

T-DXd is approved in HER2-low & ultra-low HR+/HER2- MBC after it improved outcomes in pivotal ph3 trials. ❓A role for T-DXd in HER2-low/HR+ early breast cancer? Final resuls from TALENT presented today at #ESMO26 are described & commented by @breastDoktor #ESMOAmbassadors 👇 https://t.co/hzd7KBcJk8

TALENT: neoadjuvant Tdxd in HER2-low, HR+ early breast cancer - modest activity, pCR ~7%, not improved by adding anastrozole or sequencing chemotherapy. A useful reminder that HER2-low is not the same as HER2-driven in the curative setting. #ESMO26 #ESMOAmbassadors @myESMO https://t.co/ajzGVU6sAE

Cowabunga! 🌊 Riding the Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 TALENT: neoadjuvant trastuzumab deruxtecan in luminal HER2-low tumors.
 Residual Cancer Burden 0/1: 16–17%. Tumors shrink, rarely disappear. Wrong endpoint or wrong combination? @OncoAlert @Larvol https://t.co/U9z38ZdilM

Probably first negative trial for Trastuzumab deruxtecan. Talent trial. For early stage HR positive Her2 low EBC @myESMO #esmo26 @OncoAlert https://t.co/1m62ih9PrE

TALENT trial at #ESMO26 Neoadjuvant T-DXd +/- anastrozole or sequentially with TCx4 shows modest activity in HER2-low Hr+ early BC pCR TDXd 7%, TDXd +anastroxole 3%, TDXd x 4 -> TC×4 9% High baseline levels of HER2 prot potentially associated with higher pCR rates @OncoAlert https://t.co/8P5pLJfrg6

Oral abstract #BreastCancer session at #ESMO26: updated data from the TALENT trial showing activity of neoadjuvant #TrastuzumabDeruxtecan in HER2-low HR+ disease @OncoAlert @myESMO https://t.co/Lk2cvsDAFg

TALENT—neoadj TDXd (6-8 cycles) +/- AI in HER2 low HR+ early stage breast ca ypCR // RCB TDXd 7% // 16% T-DXd/AI: 3% // 9% T-DXd→ TC: 17% // 17% Author concludes “modest” benefit; I would say “disappointing”. ypCR just isn’t the same endpoint w/ ER+ disease #ESMO26 @OncoAlert https://t.co/3jg6NTqiyH

ESMO 2026 | TALENT Trial Neoadjuvant T-DXd: modest activity in HR+/HER2-low early breast cancer. pCR rates: T-DXd: 7% T-DXd + anastrozole: 3% T-DXd → chemotherapy: 9% Adding endocrine therapy did not improve pCR, while sequential chemotherapy offered only marginal benefit. ⚠️ 3 cases of grade 2 ILD and 1 patient death. Take-home: Impressive metastatic efficacy has not translated into meaningful neoadjuvant activity. Not practice-changing. #ESMO2026 #BreastCancer #ESMO26 @OncoAlert

TALENT trial #ESMO26 Neoadjuvant T-DXd showed modest efficacy (pCR 3–9%), with limited benefit from additional therapy and potential safety concerns. https://t.co/XCmqAJXtYW

TALENT trial presented by Sara Hurvitz: Preop TDXd in HR+ HER2-low breast cancer Preop TDXd: 7% TDXd+AI: 3% TDXd-->TC: 9% Adding endocrine therapy and sequencing chemo with TDXd didn't seem to improve pCR @OncoAlert #ESMO2026 https://t.co/dArlOO4Mpa

TALENT- neoadj T-DXd in HR+/HER2-low #bcsm RCB0/1: 🔹 T-DXd alone: 16% 🔹 T-DXd + anastrozole: 17% 🔹 T-DXd → TC chemo: 17% *no pCRs w/out 8 cycles Despite high ORR ~66%, pCR LOW! We know w/ HR+ we don't get high pCRs rates, but still disappointing #ESMO26 #ESMOAmbassadors https://t.co/smlF5DmAAt

🚨 Important biomarker signal from #ESMO2026—highly relevant beyond breast cancer! In the neoadjuvant TALENT trial T-DXd achieved relatively low pCR/near-pCR rates (16–17%) in HER2-low breast cancer. Importantly, higher baseline HER2 expression was associated with better pathological response, while HER2 expression declined substantially during treatment. Could the same principle apply to perioperative enfortumab vedotin + pembrolizumab in MIBC? We urgently need to understand whether low or absent membranous NECTIN4 expression identifies patients less likely to achieve pCR—and potentially at higher risk of recurrence despite EV+pembro. Histology, quantitative membranous NECTIN4 expression, spatial heterogeneity and ctDNA dynamics should be integrated into prospective biomarker studies. @Markuseckstein3 @DrRosenbergMSK @Dr_Aggen Precision perioperative therapy must start before cycle 1—not only after cystectomy. 🔬 @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot

#ESMO26 | TALENT Neoadjuvant T-DXd showed very low pCR rates in HR+/HER2-low early breast cancer: - T-DXd: 7% - T-DXd + anastrozole: 3% - T-DXd → chemotherapy: 9% We should remember that pCR is a limited surrogate endpoint in HR+ disease. However, these results do not support T-DXd as an alternative to standard neoadjuvant chemotherapy. Moreover, given the heterogeneity of HER2-low disease, I find it unsurprising that the success of T-DXd in the metastatic setting does not translate into similar outcomes in early-stage disease, despite the lower tumor burden.

3. DASL-HiCaP: PhIII, Darolutamide + ADT + RT in very high-risk PCa (n=1106, incl BCR post-RP) - 4y MFS-CI 95% vs 88% (HR 0.42) - OS immature - ARPIs will play a bigger role in early prostate cancer (DASL-HiCaP & PROTEUS) 4/5 https://t.co/wEFefXA02T https://t.co/0rLGbfIjH7

Putting STAMPEDE, ENZARAD, PROTEUS & DASL into context with the latest #ESMO26 updates: STAMPEDE: Abiraterone-based intensification improved MFS AND OS, predominantly with RT. New #ESMO26 Decipher data suggests differential abi benefit in cN0 disease (interaction P=.01); using this to omit treatment still requires validation. ENZARAD: At 8 years, MFS was 74% vs 72% (HR 0.88; P=.34). No significant overall MFS benefit from enza + ADT/RT. The cN1/planned pelvic RT subgroup signals remain hypothesis-generating. DASL: new at #ESMO26: 1,106 patients; 96 weeks of daro v. placebo + ADT + prostate/bed AND pelvic RT. Four-year conventional-imaging MFS: 95% vs 88% (HR 0.42). Very-high-risk population, including selected postoperative patients. Interim analysis; OS immature. PROTEUS main trial: Perioperative apa + ADT improved 5-year PSMA-inclusive MFS versus ADT alone: 78.2% vs 73.5% (HR 0.80). Conventional-imaging MFS was not statistically significant. #ESMO26 post hoc PSA-response analysis adds prognostic information. PROTEUS randomized substudy: new at #ESMO26: Perioperative apa/ADT + RP/PLND (n=102) v. immediate RP/PLND (n=306). At 37.8 months’ follow-up: • 3-year EFS: 63.0% vs 41.4%; HR 0.38. • Secondary PSMA-inclusive MFS: HR 0.49; nominal P=.0193. • Subsequent postoperative RT: 20% vs 43%. The substudy strengthens a "perioperative strategy". But conventional-imaging entry followed by PSMA-inclusive endpoints matters. PSA-based EFS, conventional MFS and PSMA-inclusive MFS are different endpoints. These trials support specific intensification strategies; they cannot rank the drugs or establish RP-versus-RT superiority. The decision remains who benefits enough to justify the ENTIRE treatment burden.

Among the big news from #ESMO2026: PROTEUS companion RCT (not a substudy ¯\_(ツ)_/¯ ) comparing neoadj apa/ADT to RP alone. Impressive early results, should put to rest at least some of the objections to PROTEUS main paper. https://t.co/DTnUeyXi2D

PROTEUS at #ESMO26: first randomized data vs. upfront RP.
1 yr APA+ADT: EFS HR 0.38, MFS (conv./PSMA PET) HR 0.49, subsequent therapy at 3 yrs 35% vs 68%.
Table: substudy, NEJM main trial, LMU real-world benchmark. 
Three questions 🧵 https://t.co/uRc6zfa4L2

At #ESMO26, Alberto Briganti presented the PROTEUS substudy, reporting improved EFS with perioperative apalutamide + ADT (HR 0.38). Nicholas van As discussed key limitations and concluded that longer follow-up is needed before changing clinical practice. #ProstateCancer https://t.co/WpztxJBIPh

PROTEUS Substudy: Periop Apa + ADT with RP+PLND vs RP+PLND in HR PCa @urotoday #ESMO26 Periop APA + ADT (+ RP+PLND; n= 102) vs RP+PLND alone (n=306) 🚨EFS: HR 0.38, 95% CI 0.26–0.55 🚨MFS: HR 0.49, 95% CI 0.26–0.90 🚨TT 1st Sub Rx: HR 0.29, 95% CI 0.20–0.43 🚨All Gr Hot Flush: 64% vs 0.7%

PROTEUS substudy at #ESMO26 presented by Alberto Briganti 🇪🇸 Perioperative apalutamide + ADT vs RP + PLND alone in HR localized/LA prostate cancer (N=408, 1:3) ▪️ EFS HR 0.38 (0.26–0.55), p<0.0001 ▪️ 36-mo EFS 63% vs 41%; SOC median EFS only 19.1 mo ▪️ Benefit held after T recovery @neerajaiims @DrChoueiri @DrRanaMcKay @tompowles1 #ProstateCancer

Proteus trial subgroup analysis. Confirms the role of perioperative APA + ADT for the selective HIGH RISK LOCALIZED #prostatecancer #ESMO26 @myESMO https://t.co/8C9aWxriH8

PROTEUS substudy results at #ESMO26 Perioperative apalutamide + ADT vs surgery alone in high-risk localized #ProstateCancer EFS HR 0.38 MFS HR 0.49 Subsequent treatment at 3 years: 35% vs 68% Compelling evidence for perioperative intensification @OncoAlert https://t.co/TgMTXmwfOH

PROTEUS substudy: perioperative ADT+APA vs surgery alone, benefits in EFS, MFS and time to subsequent therapy. Reinforces this strategy as a new treatment option for high-risk prostate cancer patients. #ESMO26 https://t.co/vOb9Yw7nuX

#PROTEUS substudy of ADT-Apalutamide in high risk #prostate cancer w/ significantly positive event free survival. Salvage radiation rates half of those in control cohort. @oncoalert #esmo26 @myESMO

Esciting presentation by @Albert0Briganti ! PROTEUS substudy: adding perioperative apalutamide + ADT to surgery improved EFS in high-risk localized/locally advanced PCa (HR 0.38). Important randomized evidence for intensification! @myESMO #ESMO26 @oncoalert https://t.co/QpfB0YpW6j

🚨 #ESMO26 GU Oncology — the studies I would keep closest on the radar @OncoAlert What stands out from the @OncoAlert GU selection is how clearly the field is moving toward perioperative intensification, biomarker-driven treatment, smarter sequencing, and new mechanisms of action. 🟠 #BladderCancer VOLGA · KEYNOTE-B15 · ENERGIZE · KEYNOTE-866 🔵 #ProstateCancer DASL-HiCaP · CAPItello-281 · PROTEUS 🟢 #KidneyCancer LITESPARK-011 · LITESPARK-012 · ivonescimab · PE-PE · SWOG S2200 · XmAb819 🎯 Why this matters: these are not just isolated trial readouts. Together, they are redefining where we intensify, where we de-escalate, how we select patients, and how earlier disease settings are becoming increasingly systemic and biology-driven. For me, the most important question across all three tumors is the same: Who actually needs more treatment — and who can safely receive less? That is where GU oncology is heading. Proud to be part of this @OncoAlert faculty following the data closely at #ESMO26. @DrChoueiri @tompowles1 @neerajaiims @PGrivasMDPhD @TiansterZhang @AndreaNecchi @DrRanaMcKay @DrYukselUrun @crisbergerot @nataliagandur #OncoAlert #GUOncology #PrecisionOncology #CancerResearch

#ESMO26 | postMONARCH – Final OS Abemaciclib + fulvestrant 🆚 placebo + fulvestrant after prior CDK4/6i in HR+/HER2− advanced #BreastCancer : 
🔹 mOS 32.1 🆚 24.6 mo (HR 0.80; p=0.11) - numeric benefit, not statistically significant. simultaneously published in @Annals_Oncology 👇 🔗 https://t.co/YzOZmhaxxn
 #bcsm @myESMO @OncoAlert

🔥 Abema + fulvestrant after 1L CDK4/6i/AI improves PFS, PFS2 & time to chemo; numerical ↑OS 👉 CDK targeting remains valid post-CDK4/6i, but NOT a class effect! ✅ Abema (postMONARCH, EMBER-3), atirmociclib (FourLight-1), ribo (MAINTAIN) ⛔ Palbo (PACE, PALMIRA) #ESMO26 https://t.co/KxHmObP6Oc

At #ESMO26 rapid oral session on advanced #breastcancer @KalinskyKevin presents results from postMONARCH Abema + fulvestrant showed numeric, non significant ⬆️ OS in aBC after PD to CDK4-6i Modest PFS improvement @OncoAlert

Overall survival from phIII postMONARCH trial of abemaciclib + fulvestrant v placebo + fulv for HR+ HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy https://t.co/hYJPDj1XzG #ESMO26 @OncoAlert @KalinskyKevin @Annals_Oncology

Why does abemaciclib still work after CDK4/6i? #postMONARCH #ESMO26 • Resistance is mostly ER-driven (ESR1), so switching to fulvestrant helps
• True CDK4/6 independence (RB1 loss) is rare
• Abema ≠ palbo: CDK4-selective, some CDK2 activity, continuous dosing PFS2 & TTC HR 0.76. Modest but real. @OncoAlert @OncBrothers @Larvol

Phase III postMONARCH: Final OS Analysis #ESMO26 @KalinskyKevin Abemaciclib + fulvestrant numerically improved OS after CDK4/6i (32.1 vs 24.6 months; HR 0.80, P=0.11), without statistical significance. PFS (HR 0.78), PFS2 (HR 0.76), and time to chemotherapy (HR 0.76) favored abemaciclib.

📢 #ESMO26 | Phase III #postMONARCH 🔹 Median OS: 32.1 vs 24.6 months (+7.5 months) 🔹 HR 0.80 (95% CI 0.60–1.06) 🔹 OS numerically favored abemaciclib + fulvestrant, but did not reach statistical significance. 📌 Encouraging OS trend following CDK4/6i progression. #BreastCancer #HRpositive @KalinskyKevin

#ESMO2026 PostMonarch - change to Fulvestrant v placebo with Abema- continues to show better PFS and OS ➡️ results by ESR1 status eagerly awaited! #ESMOAmbassadors @OncoAlert Published online in @Annals_Oncology https://t.co/Bzolx5kqxi

📌 Overall survival from the phase 3 postMONARCH trial of abemaciclib + fulvestrant vs placebo + fulvestrant for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor + endocrine therapy @KalinskyKevin #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/BlMhps9Mw7

Post-monarch continue to show improvement in PFS and numerically (NS) OS #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO @KalinskyKevin https://t.co/kcc9NvB9Tv

🧬 Progression on a CDK4/6 inhibitor does not always mean the pathway is exhausted. @OncoAlert At #ESMO26, the final OS analysis of postMONARCH tested abemaciclib + fulvestrant after progression on prior CDK4/6i + endocrine therapy in HR+/HER2– advanced #BreastCancer. 📊 n=368 ➡️ Median OS: 32.1 vs 24.6 months HR 0.80 (0.60–1.06), p=0.1145 ➡️ Updated PFS: HR 0.78 (0.62–0.99) ➡️ No new safety signals The OS difference is numerically meaningful, but not statistically significant. 🎯 Why this matters: continuing CDK4/6 pathway suppression after progression may still have value — but not for every patient, and not with the same magnitude of benefit. For me, the real next step is to understand who remains biologically CDK-dependent after progression and who should instead switch to a different therapeutic pathway. That is the precision question behind postMONARCH. Excellent work from @KalinskyKevin @BianchiniGP @ErikaHamilton9 @DrSGraff @drsarahsam @MuozMateu and the investigators. Pinging @matteolambe @aftimosp @E_de_Azambuja @hoperugo @stolaney1 @kevinpunie @ElisaAgostinett @GaiaGriguolo @JankovicK @LoiSher #OncoAlert #ESMO26 #BreastCancer #CDK46 #EndocrineTherapy #PrecisionOncology

postMONARCH | ESMO 2026 CDK4/6 inhibition after progression? Abemaciclib + fulvestrant: • Original PFS: 6.0 vs 5.3 months. • Final OS: 32.1 vs 24.6 months; HR 0.80, p=0.1145. Modest PFS benefit; numerically longer OS without statistical significance. An option for selected patients. Reference: Kalinsky K et al. postMONARCH, ESMO 2026; original PFS publication, JCO. #MVOnco #ESMO2026 #BreastCancer #postMONARCH

🤩 @OncBrothers highlighting 🔑 studies presented on Day 1 of #ESMO26 #BreastCancer 1. #NATALEE 2. #HorizonBreast06 3. #TALENT #GIOnc 4. #RASolute302 5. #HerizonGEA01 #GUOnc 6. #KN866 7. #PEACE1 #OncTwitter #MedTwitter #bcsm #gism #gucsm @myESMO #MedX #MedEd #Oncology https://t.co/s1p1cmrz2k

NATALEE, NSABP B-42, PANKU-Breast01, TALENT, HERIZON-GEA-01, KEYNOTE-866 ve RASolute-302. Sağkalım faydası nerede gösterildi? Hangi çalışma primer sonlanımını karşılayamadı? Yeni verileri hasta grubu ve tedavi bağlamıyla birlikte değerlendirdik. #ESMO2026 https://t.co/gsMeDN50vu

ESMO 2026 Key late Breaking Abstracts Atypical EGFR mutation Enozertinib: Birth of Redwood 1 (2027) HERIZON-GEA-01 Her2+ GE Adenocarcinoma Zoci: ES SCLC https://t.co/Jj2g51gR06

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

🚨 #ESMO26 moves fast your inbox should help you keep up, not add more noise. @OncoAlert The daily @OncoAlert Newsletter is LIVE from Madrid 🇪🇸 and delivers the most relevant congress data straight to your inbox every morning. 📌 Day 1 highlights 🎗️ NATALEE 6-year OS 🧬 PANKU-Breast01 + Lancet publication 🟠 KEYNOTE-866 & ENERGIZE two important negative MIBC trials 🟣 HERIZON-GEA-01 3-year OS 🎯 Why this matters: congress coverage is not about reading everything. It is about identifying the data that deserve attention, understanding what they mean, and moving quickly from headline to clinical context. That is what @OncoAlert does best: Less noise. More signal. Science that matters. 🤝 For colleagues, by colleagues. 📩 Register FREE: https://t.co/NFi1ia680V 👉 Subscribe: https://t.co/kHfE8oDWmE @DrChoueiri @PGrivasMDPhD @AndreaNecchi @TiansterZhang @hoperugo @stolaney1 @christine_lovly @CathyEngMD @BenWestphalen @nataliagandur #OncoAlert #ESMO26 #Oncology #CancerResearch #MedicalEducation

🚨 Day 1 highlights from #ESMO26 are here! Subscribe for FREE 👉 https://t.co/Q2y6eL4mxY From NATALEE and PANKU-Breast01 to KEYNOTE-866, ENERGIZE & HERIZON-GEA-01 - stay updated with @OncoAlert, straight to your inbox every morning! 📩 https://t.co/ojhxebvmd6

HERIZON-GEA-01 at #ESMO26: Zanidatamab + chemotherapy improved PFS and OS versus trastuzumab-based therapy in 1L HER2+ advanced GEA. The triplet regimen with tislelizumab achieved a median OS of 27 months and a 3-year OS rate of 40%. @OncoAlert #HER2Positive https://t.co/U7iPdH0TRg

Zanidatamab + CT ± tislelizumab for 1L HER2-positive mGEA: Second IA from HERIZON-GEA-01 #ESMO26 #ESMOAmbassadors 👉 mOS: 27 vs22.9 vs 19.6 mo 🧐Continued meaningful benefit for Zani & Tis independent of PDL-1 @myESMO @ASCO https://t.co/s1YjgvtQel

#ESMO26 | HERIZON-GEA-01 – Updated OS Her2 positive gastric/ge cancer At 35.3 months of follow-up, zanidatamab + CT now shows a significant OS benefit over trastuzumab + CT: 22.9 vs 19.6 months (HR 0.76; p=0.0088). With the addition of tislelizumab, median OS increased to 27 months, but the additional benefit was statistically borderline (HR 0.81; p=0.0502). Considering toxicity, we need to carefully analyze which patients should receive the triplet regimen.

🚀Upper GI oral abstracts #ESMO26 Day 1 summary results 1) Arcotatug tavatecan improved PFS in CLDN18.2+ G/GEJA in the 3L+ setting 2) SANO trial, OS at 5 years similar between active surveillance and surgery in patients with oesophageal cancer and a complete clinical response after nCR, despite more distant metastasis 3) Adding pembrolizumab to dCRT did not improve EFS in untreated unresectable esophageal or GEJ cancer with PD-L1 CPS ≥10 4) Daraxonrasib demonstrated consistent OS benefit in different RAS mutatin subgroups in RASolute-302 5) mKRAS-specific lymph node targeted amphiphile immunotherapy in PDAC did not met primary DFS endpoint. 6) Zani + CT +/- tisle keep OS benefit in at IA2 of HERIZON-GEA-01 7) Anbenitamab plus ChT improved OS in patients with HER2-positive GC/GEJC adenoca after previous trastuzumab 8) TQB2102 (HER2 bispecific antibody-drug conjugate) plus bemotrizumab and capecitabine demonstrates promising antitumor activity in 1L of advanced GC/GEJC 9) Dostarlimab in Pts with localized dMMR/MSI-H GEA led to a 62.5% 1y-cCR at the first interim analysis, enabling organ preservation. 10) FOLFIRI and Ram vs paclitaxel in taxan-pretreated GEA imporved PFS but no OS 11) Stage II–IIIB gastric cancer after D2 resection, four months of adjuvant XELOX was noninferior to six months for 3-year DFS 12) Adding durvalumab to dCRT in locally advanced esophagus carcinoma did not improve PFS 13) Adding SBRT to MFOLFIRINOX in high risk, borderline resectable or locally advanced pancreatic cancer mproved LRR and PFS 14) FGFR2b expressing GC/GEJ with co-existing FGFR2 amp may define a biologically distinct subset with potential sensitivity to bemarituzumab #cancer #oncology #MedX #GI #gastrointestinal @OncoAlert

#ESMO26 | LBA79 Second interim analysis from Ph3 HERIZON-GEA-01 Overall survival ▪️Zani + chemo vs Tra + chemo: 22.9 vs 19.6 mo, HR 0.76, p=0.0088 ▪️Zani + Tis + chemo vs Zani + chemo: 27.0 vs 22.9 mo, HR 0.81, p=0.0502 @myESMO @OncoAler https://t.co/n8UbjHSTxt

SANO 5-year results at #ESMO2026: Overall survival was 50% with active surveillance vs 54% with surgery after complete response to neoadjuvant CRT. Distant metastases were higher (46% vs 29%), while 43% avoided non-beneficial esophagectomy. https://t.co/t39hAlesWq @myESMO https://t.co/wnYZr8hPC9

Similar five-year survival — but seventeen more patients in a hundred develop distant metastases under active surveillance. SANO (LBA78, #ESMO26) Surgery As Needed for Oesophageal cancer; multicentre stepped-wedge cluster-randomised non-inferiority phase 3 after CROSS-style neoadjuvant chemoradiotherapy and complete clinical response. @Annals_Oncology @myESMO @OncoAlert @ErasmusMC

SANO 5Y : AS after nCRT showed no statistically significant OS difference vs immediate esophagectomy (50% vs 54%), but distant metastases were higher (46% vs 29%). Organ preservation is promising, but careful selection and rigorous surveillance are essential. #ESMO2026 https://t.co/mDFE7lJShi

Sano trial; No significant OS difference does not establish equivalence!!!! Higher 5-year distant metastasis incidence with active surveillance (46% vs 29%; p<0.01) is clinically concerning and deserves attention!!! @myESMO @OncoAlert #ESMO26 @OncoAlert @Larvol https://t.co/5z1HPV3WXx

🚨 ESMO 2026 | SANO Trial – 5-Year Results Can surgery be safely omitted after cCR in oesophageal cancer? 📊 DFS: HR 1.39 (p=0.10) ⚠️ Distant metastases: 40% vs 23% (p<0.01) ⚠️ Cancer mortality: sHR 1.67 (p=0.04) ✅ 43% potentially avoided surgery. Careful patient selection!! https://t.co/d6H5wmysHC

#ESMO26 🔬 SANO | 5-year outcomes 👥 309 pts with cCR after nCRT ⚖️ Active surveillance vs surgery 📈 OS: HR 1.17 (p=0.46) 📊 DFS: HR 1.39 (p=0.10) ⚠️ Distant dissemination: 46% vs 29% (sHR 2.04; p<0.01) 🏥 43% potentially avoided esophagectomy 💡 Organ preservation, but higher metastatic risk. @OncoAlert

SANO trial: Active surveillance vs standard surgery after neoadjuvant chemoradiotherapy for oesophageal cancer: Long-term results #ESMO26 #ESMOAmbassadors 👉 DFS HR: 1.39 👉 OS HR:1.17 👉Distant mets: sHR 2.04 🧐OS not different, supports consideration of active surveillance @myESMO @ASCO

🔥 SANO 5-year results🔥 Esophagus cancer 👥 309 pts with cCR after nCRT 🔍 Surveillance vs surgery ✅ 5y OS: 50% vs 54% (HR 1.17) ⚠️ Distant mets: 46% vs 29% (P<.01) 💥 43% organ preservation Active surveillance remains a feasible strategy albeit we must recognize the DM risk despite no OS difference. Perhaps TNT, like D-FLOT ➡️CRT with subsequent AS for cCR may be an optimal next strategy to test. Improved response assessment strategies also needed #ESMO26

🚨 #ESMO26 | SANO Trial (LBA78) Can we skip surgery after complete response to neoadjuvant CRT in oesophageal cancer? 5-year outcomes (n=309): 🔹 OS: 50% vs 54% (HR 1.17) 🔹 Distant metastases: 46% vs 29% (p<0.01) 🔹 43% spared non-beneficial oesophagectomy. 🎯 Verdict: Active surveillance offers organ preservation without a statistically significant OS difference, but higher distant metastases raise concern. Could surveillance become a standard option for carefully selected patients? @ESMO_open @my_esmo @ASCO @oncoalert #SANO #EsophagealCancer

🚀Upper GI oral abstracts #ESMO26 Day 1 summary results 1) Arcotatug tavatecan improved PFS in CLDN18.2+ G/GEJA in the 3L+ setting 2) SANO trial, OS at 5 years similar between active surveillance and surgery in patients with oesophageal cancer and a complete clinical response after nCR, despite more distant metastasis 3) Adding pembrolizumab to dCRT did not improve EFS in untreated unresectable esophageal or GEJ cancer with PD-L1 CPS ≥10 4) Daraxonrasib demonstrated consistent OS benefit in different RAS mutatin subgroups in RASolute-302 5) mKRAS-specific lymph node targeted amphiphile immunotherapy in PDAC did not met primary DFS endpoint. 6) Zani + CT +/- tisle keep OS benefit in at IA2 of HERIZON-GEA-01 7) Anbenitamab plus ChT improved OS in patients with HER2-positive GC/GEJC adenoca after previous trastuzumab 8) TQB2102 (HER2 bispecific antibody-drug conjugate) plus bemotrizumab and capecitabine demonstrates promising antitumor activity in 1L of advanced GC/GEJC 9) Dostarlimab in Pts with localized dMMR/MSI-H GEA led to a 62.5% 1y-cCR at the first interim analysis, enabling organ preservation. 10) FOLFIRI and Ram vs paclitaxel in taxan-pretreated GEA imporved PFS but no OS 11) Stage II–IIIB gastric cancer after D2 resection, four months of adjuvant XELOX was noninferior to six months for 3-year DFS 12) Adding durvalumab to dCRT in locally advanced esophagus carcinoma did not improve PFS 13) Adding SBRT to MFOLFIRINOX in high risk, borderline resectable or locally advanced pancreatic cancer mproved LRR and PFS 14) FGFR2b expressing GC/GEJ with co-existing FGFR2 amp may define a biologically distinct subset with potential sensitivity to bemarituzumab #cancer #oncology #MedX #GI #gastrointestinal @OncoAlert

#ESMO26 | LBA78 Long-term results from SANO: Active surveillance vs standard surgery after nCRT in EC ▪️5y-OS: 50% vs 54%, HR 1.17 (95% CI 0.77-1.77) ▪️DFS: HR 1.39 (95%CI 0.94-2.06) ▪️5y-distant mets: 46% vs 29%, p<0.01 👉Despite no significant OS or DFS differences, the wide CIs and significantly higher distant mets rate highlight important challenges for implementing active surveillance in clinical practice. Looking forward to the presentation! @myESMO @OncoAlert

🚨 SANO | ESMO 2026 | LBA78 SAVE THE OESOPHAGUS. BUT AT WHAT COST? Can we safely avoid oesophagectomy after complete clinical response to neoadjuvant chemoradiotherapy? 🔹 SANO 5-year results (N=309) Active surveillance vs surgery: • 5-year OS: 50% vs 54% (HR 1.17) • DFS: HR 1.39 • Distant metastases: 46% vs 29% (P < 0.01) • 43% avoided an oesophagectomy classified as non-beneficial. ⚠️ The paradox: No statistically significant OS difference, yet 17 percentage points MORE distant metastases with surveillance. TAKE-HOME Organ preservation is feasible in selected patients, but long-term oncological equivalence remains uncertain. Careful selection, intensive surveillance and access to salvage surgery are essential. Are we preserving the oesophagus at the cost of distant disease control? 📖 Ref: Gangaram-Panday SS et al. SANO trial: 5-year results. ESMO 2026; LBA78. #MVOnco #ESMO2026 #SANO #EsophagealCancer #Oncology

🚨 ESMO 2026 | SANO Trial (LBA78): 5-Year Result Active surveillance vs surgery (N=309) 🔹 5-year OS: 50% vs 54% (HR 1.17; 95% CI 0.77–1.77) 🔹 DFS: HR 1.39 (95% CI 0.94–2.06) 🔹 5-year distant metastases: 46% vs 29% (p<0.01) 🔹 43% in the surveillance arm were spared a non-beneficial oesophagectomy. An important organ-preservation strategy, but the higher distant metastasis rate is concerning. Would you recommend active surveillance over surgery for a patient achieving complete clinical response? #ESMO26 #EsophagealCancer #SANO @myESMO @NiuSanford @OncoAlert @OncBrothers

🚨SANO 5y: surveillance vs surgery after cCR OS 50% vs 54% (NS) Distant mets 46% vs 29% (P<.01) Reminder: only 41.4 Gy/23 fx, a pre-op, arguably non-definitive dose, especially with/ ~75% adenocarcinoma. Nonsignificant OS doesn't establish noninferiority. #ESMO26 #RadOnc #OncTwitter

🌟AND finally, #ESMO26 wouldn't be complete without some of the HEAVY hitters. I expect these data to change practice! 1⃣Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial. I fully expect this trial to establish DLL3 TCE as the dominant first line strategy in SCLC and will likely be practice changing. 2⃣Krascendo 1: Efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. Given the evolution of KRAS G12Ci in this space, what is notable here is the direct prospective comparison to current KRAS G12Ci (adagrasib / sotorasib). Looking forward to ascertain magnitude of potential benefit and safety differences. 3⃣INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL) Technically not a lung cancer study, but I believe this trial to be game-changing from a proof-of-concept approach. In my mind, this study establishes personalized mRNA-based approaches as a viable approach and worthy of research and clinical investment. @lcsmchat @OncoAlert @OncLive @Onco_Nexus @LungCancerEu @Lung_Cancers @LungCancerRx @MedwatchHQ @KRASKickers @SclcSMASHERS @YoungLungCancer

Encouraging progress for patients with KRAS G12C-mutated lung cancer. Head-to-head studies like KRASCENDO-1 can help physicians better understand which targeted therapies offer patients the greatest benefit. Timely molecular diagnostics will play an increasingly important role in matching patients with the right treatments. Looking forward to Dr. Skoulidis’s presentation at #ESMO26.

🚨 #ESMO26 Lung Cancer: the 10 studies that best capture where the field is moving @OncoAlert What stands out to me from the @OncoAlert faculty selection is how much the lung cancer landscape is shifting toward smarter sequencing, biomarker-defined combinations, and more selective treatment intensification. 🫁 Top Ten from Madrid: 1️⃣ DeLLphi-305 — tarlatamab + durvalumab in 1L ES-SCLC maintenance 2️⃣ Krascendo 1 — divarasib vs sotorasib/adagrasib in KRAS G12C NSCLC 3️⃣ SAFFRON — osimertinib + savolitinib after osimertinib in EGFRm/MET+ disease 4️⃣ OptiTROP-Lung04 — sac-TMT after EGFR-TKI 5️⃣ OptiTROP-Lung06 — sac-TMT + pembrolizumab in PD-L1-negative NSCLC 6️⃣ PERSEE — pembrolizumab ± chemotherapy in PD-L1 ≥50% 7️⃣ SANOVO — savolitinib + osimertinib in 1L EGFRm/MET-overexpressed NSCLC 8️⃣ IFCT-2103 DIAL — continue pembrolizumab vs observation at 6 months 9️⃣ PANKU-Lung01 — iza-bren after third-generation EGFR TKI 🔟 SARON — consolidation RT in oligometastatic NSCLC 🎯 Why this matters: these studies are not just adding new drugs. They are refining when to intensify, when to combine, when to continue, and when biology should drive the next step. That is the real value of a “Top Ten” list: not more information — better prioritization of the data most likely to influence practice. @christine_lovly @GlopesMd @DrSanjayPopat @StephenVLiu @jillfeldman4 @UOzkerim @DrMirallas @CharuAggarwalMD @peters_solange @JordiRemon #lcsm #OncoAlert #ESMO26 #LungCancer #NSCLC #SCLC #PrecisionOncology

@myESMO @LungCancerRx @OncoAlert @oncodaily 4/ Krascendo 1 (LBA5), Oct 25, 16:30 CET Divarasib vs sotorasib or adagrasib, pretreated KRAS G12C NSCLC. Roche reports PFS + OS wins. How wide is the gap within the G12C class, and at what tolerability? @LungCancerRx @OncoAlert @oncodaily https://t.co/bq3FpEdrj8

NATALEE, NSABP B-42, PANKU-Breast01, TALENT, HERIZON-GEA-01, KEYNOTE-866 ve RASolute-302. Sağkalım faydası nerede gösterildi? Hangi çalışma primer sonlanımını karşılayamadı? Yeni verileri hasta grubu ve tedavi bağlamıyla birlikte değerlendirdik. #ESMO2026 https://t.co/gsMeDN50vu

@Rodrosb @myESMO I see the benefit in high-risk, node-positive patients, especially after the NSABP B-42 data presented at #ESMO26. However, I have more doubts about the N0 population in NATALEE. Great topic!@Rodrosb

NSABP B-42 Curious to see which subgroups, beyond nodal status, may benefit from extending AI therapy to 10 years! #ESMO26 https://t.co/qopzFS9DCI

NSABP B-42 (15-year data): #ESMO26 Extended letrozole reduces distant recurrence, but without a significant OS benefit. 🔹 Node-positive: 4.4% absolute benefit 🔹 Node-negative: 1.6% (not statistically significant) @OncoAlert #BreastCancer #bcsm https://t.co/BRlrSNdzPp

Cowabunga! 🌊 Riding the Early & Adjuvant Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 NSABP B-42, 15 yrs: 5 more years of letrozole. Distant recurrence 6.9% vs 9.7%, no survival gain. Extend by risk, not by default, using nodes and possibly genomic tools. @OncoAlert https://t.co/PJTqIACpsr

#ESMO26: NSABP B-42 at 15 years: extended letrozole continues to improve DFS, with particular relevance for patients with node-positive disease. No statistically significant OS benefit at 15 years, although a trend toward fewer breast cancer deaths is encouraging.

15-year results of NSABP B-42 confirm that extended letrozole results in - improved DFS - reduced Distant Recurrence - no sign difference in OS (trend for BC related deaths, but most deaths were non -BC related) No increase in fractures / thrombotic events @OncoAlert #ESMO26 https://t.co/64j6k20Rks

Great to see updated NSABP B42. Sustained benefit for extended endocrine Rx. One of many studies brought to Ireland by ICORG. @BrianCMoulton deserves credit for forging international collaborations. #ESMO26 #ESMO206. Great to see Janice Walshe as co-author.

15-year results from NSABP B42. Extended AI after prior AI therapy led to a small yet significant advantage in 15y recurrence rate, mostly seen in node-positive disease (DRFS delta 4.4% N+, vs 1.6% N-). Important data to inform pts when deciding whether to extend ET. #ESMO26 https://t.co/0VzJWBa6BB

Oral abstract #BreastCancer session at #ESMO26: updated 15-y results from @NSABPFoundation NSABP B42 trial on extended #letrozole in post menopausal women with HR+ disease @OncoAlert @myESMO https://t.co/PggpBYOkFQ

Final analysis of NSABP B-42 - mFu 15.9 years - extended ET continue to improve DFS, BCFi, distant recurrences. Similar OS and osteoporotic fractures and TVE #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/XtgiBsXB1W

#ESMO26 | NSABP B-42 – 15-year final analysis After 5 years of AI-based therapy, an additional 5 years of letrozole: • DFS: 61.6% vs 56.5% (HR 0.85). • Distant recurrence: 6.9% vs 9.7% (HR 0.72). The sustained reduction in distant recurrence is valuable. Given changes in post-recurrence treatment over such a long follow-up, I do not consider OS alone decisive. However, SALSA did not demonstrate superiority of 10 over 7 years, nor did IDEAL demonstrate superiority of 10 over 7.5 years. B-42 compares 5 with 10 years. Several questions remain: • In which patients is 10 years superior to 7–8 years? • Should we go beyond 10 years? • When adjuvant CDK4/6 inhibitors are added, should we still extend endocrine therapy for this long? Personally, I favour extending treatment to 10 years, particularly in patients at high risk of late recurrence who tolerate therapy well, and perhaps longer in selected patients.

Older adults at #ESMO26: MOIO (LBA10) on 3-monthly checkpoint inhibitors, TOP-1 (545RO) on omitting RT in older women with ER+ breast cancer, B-42 (LBA24) on extended letrozole, EV-302 in older patients (4761P). De-escalation is the theme this year. #GeriatricOncology #gerionc @myESMO @SIOGorg @siognah @SIOGnursing_AH @YoungSIOG @AlumniSiog @royalmarsdenNHS @ICR_London @royalmarsden

🧠 CNS activity of a TROP2 ADC in a randomized phase 3. #ESMO26 LBA96: brain mets analysis of TROPION-Breast02, Dato-DXd vs chemo in 1L TNBC patients who are not IO candidates. 🧵 #bcsm 61 of 644 patients had asymptomatic, stable brain mets (30 untreated, 31 previously treated). 24 had measurable intracranial disease. 🙌🏻 Intracranial response: ORR 62.5% vs 37.5%, including a complete response 12-week intracranial disease control 75% vs 50% 🙌🏻 CNS PFS 9.5 vs 2.6 mo, HR 0.27 (95% CI 0.13–0.56). Systemic PFS in the brain mets group: 7.7 vs 3.5 mo, HR 0.37. The signal held in *untreated* brain mets: PFS HR 0.29, OS HR 0.35. That's the group where systemic options matter most. Bottom line: Dato-DXd is a reasonable systemic choice for 1L TNBC with brain mets.

🧠 #TROPIONBreast02 at #ESMO26 🇪🇸 In 1L mTNBC with brain metastases, Dato-DXd showed promising systemic and intracranial activity 🆚 chemo: 🔹 CNS PFS: 9.5 vs 2.6 months (HR 0.27) 🔹 Intracranial ORR: 62.5% vs 37.5% in measurable disease @OncoAlert @myESMO https://t.co/Ncc4N6yEqk

TROPION-Breast02 #ESMO26 In 1L mTNBC with brain metastases, Dato-DXd showed promising intracranial and systemic activity vs chemotherapy: • CNS PFS: 9.5 vs 2.6 months (HR 0.27) @OncoAlert #BreastCancer #Bcsm https://t.co/IfL8AktwcJ

TROPION-Breast02 brain mets analysis at #ESMO26 (Dent). 1L Dato-DXd vs chemo, mTNBC, n=61 with BMs: CNS PFS 9.5 vs 2.6 mo, HR 0.27 
icORR (measurable) 62.5% vs 37.5% 
Untreated BMs: OS HR 0.35
Longest icDoR ~27 mo Preferred Trop2 ADC for brain Mets! @RebeccaDSing Exploratory, small n, real CNS signal. #bcsm

Important data presented at #ESMO2026 TROPION-Breast02 | 1L mTNBC with brain metastases • Median CNS PFS: 9.5 vs 2.6 months (HR 0.27) • Intracranial ORR: 62.5% vs 37.5% Dato-DXd showed great activity, regardless of prior CNS-directed therapy in TNBC @OncoAlert https://t.co/M84knqaYE0

ESMO 2026 | Can ADCs overcome the blood–brain barrier? TROPION-Breast02: Dato-DXd vs chemotherapy in metastatic TNBC with brain metastases. • CNS PFS: 9.5 vs 2.6 months (HR 0.27) • Intracranial ORR: 62.5% vs 37.5% Promising intracranial activity, although subgroup findings remain exploratory. #ESMO26 #TNBC #ADC @myesmo @oncodaily @OncoAlert @OncoDailyBreast @OncBrothers @PTarantinoMD

Promising CNS activity with Dato-DXd! #TROPIONBreast02: In 61 patients with mTNBC & asymptomatic brain metastases, median CNS PFS was 9.5 vs 2.6 months with chemo (HR 0.27). Included patients without prior CNS-directed therapy—a key strength. #ESMO26 #BCSM @Larvol @OncoAlert https://t.co/X3K0Pr45xT

#ESMO26 | TROPION-Breast02 – CNS Analysis In 1L mTNBC with asymptomatic brain metastases, Dato-DXd vs chemotherapy demonstrated: Promising intracranial activity, including in patients without prior CNS-directed therapy. https://t.co/k71kbE1Wln

Oral abstract #BreastCancer session at #ESMO26: more data from TROPIONbreast02 trial presented by super @RebeccaDSing showing important CNS activity of #DatopotomabDeruxtecan in patients with triple-negative advanced disease @OncoAlert @myESMO https://t.co/lc4QVllaGm

Dato-dxd shows an intracranial ORR of 62.5 % and median CNS PFS of 9.5 mos in pts with brain metastases (TROPiON-Breast02) #ESMO26 #ESMOAmbassadors #ESMOcommunity @esmo @RebeccaDSing https://t.co/Q7Zj5mqdva

TROPIONBreast02 DatoDXd vs TPC chemo in 1L mTNBC brain Mets analysis by @RebeccaDSing Allowed treated or untx + asymptomatic brain mets (n=61) Intracranial response 62.5% vs 37.5% w/ durable benefit at 12 weeks 75% vs 50% #ESMO26 @OncoAlert https://t.co/HguoAefquz

At #ESMO26 Proffered Paper 2️⃣ on #breastcancer Exploratory analysis of Tropion-Breast02 by @RebeccaDSing focusing on pts with brain mets 🧠 Dato-DXd showed consistent systemic (PFS, OS, ORR) and intracranial benefit (icORR, CNS-PFS) vs. TPC in pts with brain mets @OncoAlert https://t.co/fWbXavgiOB

TROPION-Breast02 CNS fabulously presented by @RebeccaDSing n=61 with baseline brain mets n=35 on Dato-DXd arm (16 had prior treatment for brain mets) PFS HR 0.37, OS HR 0.55 iORR: 62.5% vs 37.5% @OncoAlert #ESMO26 https://t.co/XHUe50PHDU

Three new ADCs at ESMO 2026, three targets: HER2 (TQB2102, APEX-Breast01), EGFR x HER3 (iza-bren, PANKU-Breast01), nectin-4 (SHR-A2102, cervix). One payload: TOPO1 inhibitor. In cervix, the approved ADC is tisotumab, an MMAE payload, so a TOPO1 ADC after it is a real mechanism switch. In breast after T-DXd, a new target on the same payload is a different bet, and cross-resistance is the open question. The trial I want randomizes by payload sequence, not by target. #gyncsm #ESMO26 @myESMO

Impressive #APEXBreast01 data showing benefit with rolditamig deuderuxtecan over first-line chemotherapy in HR+/HER2-low metastatic #BreastCancer! 📌 mPFS: 16.4 vs 5.5 months (HR 0.29) 📌 ORR more than doubled 📌 Encouraging early OS trend #ESMO26 @OncoAlert https://t.co/B5RgQQ1xwc

Three HER2 ADCs now in HER2-low MBC. At #ESMO26, HORIZON-Breast06 & APEX-Breast01 both beat chemo on PFS (HR ~0.25–0.29). But as @BarbaraPistill2 noted: same payload class as Tdxd, tested vs chemo not the standard. Head-to-head ADC trials needed. #ESMOAmbassadors @myESMO https://t.co/Yntya2iiR3

APEX-Breast01: #ESMO26 TQB2102 Delivers a Substantial PFS Benefit in HER2-Low Metastatic Breast Cancer, With OS and Long-Term Safety Still to Mature @OncoAlert #BreastCancer #Bcsm https://t.co/B5z8hNKLPb

First breast session at #ESMO26 highlights how China is developing novel drugs at rapid speed. Positive PFS results with HER2-directed ADCs (HORIZON-Breast06 + APEX-Breast01), but neither compare to current SoC of T-DXd. Fights for market share, but does it push the needle?

Oral abstract #BreastCancer session at #ESMO26: impressive data from APEXbreast01 trial showing benefit for #RolditamigDeuderuxtecan as first line chemotherapy in advanced HER2-low metastatic disease @OncoAlert @myESMO https://t.co/NJo4nAjHEY

APEX Breast01 TQB2102 (biapotropic ADC against HER2 with topo1 payload) Rolditamig Deuderuxtecan (TQB2102) vs TPC Chemo in HER2low MBC, no prior chemo (461 HR+, 81 TNBC) PFS HER2low: 16.4 vs 5.5 mo, HR 0.29 ILD 1.1% @OncoAlert #ESMO2026 https://t.co/tTbO5g3ofI

APEX-Breast01 Rolditamig DXd (TQB2102, a biparatopic ADC) vs TPC chemo in HER2-low MBC has meaningful efficacy median PFS 16.4 vs 5.5 mo HR=0.29 OS HR=0.44 ORR 68.8% vs 31.0% #ESMO26 https://t.co/kMiu6UA14O

APEX-B01 at #ESMO26 TQB2102 (biparatopic anti-HER2 ADC with Topo1inh) vs CT in patients with HER2-low mBC not previously treated with CT Significantly improved PFS Improved OS @OncoAlert https://t.co/OJeNp4sc3d

🇨🇳 TQB2102 (biparatopic HER2 TOPO1 ADC) also passes the truck test in mostly HR+/HER2-low MBC. PFS 16.4 vs 5.5 mo, HR 0.29, p<0.01. Unclear whether the biparatopic design adds anything. The HER2 TOPO1 field is getting quite crowded with excellent agents. #ESMOAmbassadors #ESMO26 https://t.co/nOV5QhN7PR

At #ESMO26 proffered paper session 1️⃣ on #breastcancer TQB2102, a novel biparatopic HER2-targeting antibody-drug conjugate, ⬆️ PFS versus TPC in pts with HER2-low, chemo-naive mBC @OncoAlert https://t.co/mG8Uxk8X0x

Cowabunga! 🌊 Riding the Metastatic Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 APEX-Breast01: biparatopic HER2 antibody-drug conjugate TQB2102 vs chemo in HER2-low disease. Progression-free survival 16.4 vs 5.5 mo. New ADC, same ~0.3 hazard ratio. Time for head-to-head trials. @OncoAlert @Larvol

TQB2102 imporoves PFS in chemo naive HR + HER2 low MBC - OS trend - low ILD rate #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/WBAxxdSUBX

🤩 @OncBrothers highlighting 🔑 studies presented on Day 1 of #ESMO26 #BreastCancer 1. #NATALEE 2. #HorizonBreast06 3. #TALENT #GIOnc 4. #RASolute302 5. #HerizonGEA01 #GUOnc 6. #KN866 7. #PEACE1 #OncTwitter #MedTwitter #bcsm #gism #gucsm @myESMO #MedX #MedEd #Oncology https://t.co/s1p1cmrz2k

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

Three HER2 ADCs now in HER2-low MBC. At #ESMO26, HORIZON-Breast06 & APEX-Breast01 both beat chemo on PFS (HR ~0.25–0.29). But as @BarbaraPistill2 noted: same payload class as Tdxd, tested vs chemo not the standard. Head-to-head ADC trials needed. #ESMOAmbassadors @myESMO https://t.co/Yntya2iiR3

First breast session at #ESMO26 highlights how China is developing novel drugs at rapid speed. Positive PFS results with HER2-directed ADCs (HORIZON-Breast06 + APEX-Breast01), but neither compare to current SoC of T-DXd. Fights for market share, but does it push the needle?

HORIZON-Breast06 confirms benefit of trastuzumab *rezetecan* in a DB06-like patient population—HER2low, chemo-naive #ESMO26 @OncoAlert https://t.co/oQ56NjDGq4

HORIZON-Breast06: Trastuzumab Rezetecan in HER2-Low Metastatic #BreastCancer — A Major PFS Benefit, With OS and Long-Term Safety Requiring Further Follow-Up @OncoAlert #ESMO26 @myESMO #Bcsm https://t.co/X8ZCODantr

🚨 ESMO 2026 | HORIZON-Breast06 (Phase III) Impressive results with trastuzumab rezetecan (HER2 ADC) vs physician’s choice chemo in HER2-low mBC. 🔹 mPFS: 16.6 vs 6.8 mo (HR 0.25; P<0.001) in chemo-naïve pts 🔹 ORR: 76% vs 43.3% 🔹 HR+: mPFS 16.4 vs 6.7 mo (HR 0.24) 🔹 HR−: mPFS 16.5 vs 6.8 mo (HR 0.34) 🔹 mDoR: 15.3 vs 6.9 mo ⚠️ Toxicity: Significant G≥3 myelosuppression (anemia 42.8%, neutropenia 65.2%, thrombocytopenia 35.9%). ILD reported in 2.5% (any grade). #ESMO26 #BreastCancer #HER2Low #ADC @OncoAlert #bcsm

Cowabunga! 🌊 Riding the Metastatic Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 HORIZON-Breast06: trastuzumab rezetecan vs chemo in HER2-low disease. Progression-free survival 16.4 vs 6.8 mo, hazard ratio 0.27. HER2-low is ADC territory now. Which antibody-drug conjugate, and when? @OncoAlert @Larvol

Oral abstract #BreastCancer session at #ESMO26: simultaneously published @JAMA_current results from #HORIZONbreast06 trial showing impressive activity of #TrastuzumabRezetecan in patients with HER2-low advanced disease @OncoAlert @myESMO https://t.co/S3SPEIW9ih

🇨🇳HORIZON-Breast06: Trastuzumab rezatecan widely outperformed chemo in endocrine-refractory HR+ MBC (PFS 16.6 vs 6.8 months, HR 0.25, p=0<0.01). Definitely passes the truck test. No significant OS, likely due to crossover of some patients to TOPO1 ADCs. #ESMO26 #ESMOAmbassadors https://t.co/u7TsssjoiN

HORIZON-Breast06: Trastuzumab rezetecan in metastatic HER2low breast cancer n=551 PFS chemo-naive: 16.6 vs 6.8 mo HR 0.25 PFS consistent in HR+ vs HR- (HR 0.34 and HR 0.24) OS immature ILD 2.5% @OncoAlert #ESMO2026 https://t.co/SwCRjdV8MO

#ESMO26 | HORIZON-Breast06 HER2-low mBC after ≥1 prior line of chemo for metastatic disease, or in the first-line chemo setting after prior ET (if HR+). Trastuzumab rezetecan vs. physician’s choice of chemo PFS: 16.4 vs 6.8 mo (HR 0.27) ORR: 75.5% vs 41.2% Grade ≥3 TRAEs: 84.1% vs 67.9% ILD: 2.5%.

Exciting phase 3 trials data in metastatic #ProstateCancer @myESMO #ESMO26 #ESMOAmbassadors #PEACE1 #Capitello281 @Silke_Gillessen @neerajaiims @OncoAlert @OncBrothers @PCFnews @shilpaonc @EAntonarakis @Parminder1699 @Uromigos @montypal @docjavip @drenriquegrande @cdanicas https://t.co/epveHRbSgb

Long-term OS with AA/P in the PEACE-1 trial for de novo mCSPC @urotoday #ESMO26 mFU: 7.7 yrs 🚨SOC (+/-RT) + Abi vs SOC (+/-RT): abs OS ⏫ 1.5 yrs (HR 0.75, 95.1% 0.65-0.87) 🚨ADT + Doce + Abi vs Abi + ADT: abs OS ⏫ 1.8 yrs (HR 0.68, 95.1% CI 0.56-0.82) 🚨Favorable effect of triplet Rx on OS, independent of vol disease (interaction test p=0.56)

🚨⭐🔵 #ESMO26 | Abstract 2215O | PEACE-1 Long-term overall survival with abiraterone acetate plus prednisone in the PEACE-1 phase 3 trial for de novo metastatic castration-sensitive prostate cancer (mCSPC) 🎤 Presented by Prof. Karim Fizazi 🇫🇷 @OncoAlert @myESMO 🔬 7.7 years of follow-up: Does upfront treatment intensification translate into durable survival? PEACE-1 provides a compelling answer! 📊 PHASE III | N=1,173 Randomized 2×2 factorial design evaluating abiraterone + prednisone and/or prostate radiotherapy added to standard of care (ADT ± docetaxel). Median follow-up: 7.7 years. 📈 1️⃣ OVERALL POPULATION ✅ OS HR 0.75 (95% CI 0.65–0.87) ✅ p=0.0001 Median OS: 🔹 With abiraterone: 6.1 years 🔹 Without abiraterone: 4.6 years ➡️ A sustained 25% relative reduction in the hazard of death. 💥 2️⃣ TRIPLET THERAPY | N=710 ADT + docetaxel + abiraterone vs ADT + docetaxel: ✅ Median OS: 6.2 vs 4.4 years ✅ HR 0.68 (95% CI 0.56–0.82) ⭐ 1.8 additional years in median survival! 📊 8-YEAR OVERALL SURVIVAL ✅ Triplet: 40.3% 🔹 Doublet: 27.1% ➡️ Absolute difference: +13.2 percentage points. These are clinically meaningful long-term outcomes, beyond early response rates or surrogate endpoints. 🔬 3️⃣ DOES METASTATIC VOLUME MATTER? 🔵 HIGH-VOLUME DISEASE ✅ Median OS: 4.6 vs 3.5 years ✅ HR approximately 0.68 A clear and durable survival advantage. 🔵 LOW-VOLUME DISEASE 📈 Median OS: 7.8 vs 6.2 years HR 0.74 (95% CI 0.52–1.05) Numerically favorable, although the subgroup CI crossed 1. 📌 No significant interaction by disease volume (p=0.56). ⚠️ This does not establish identical treatment benefit in both subgroups. ⭐ MY POINT OF VIEW | CLINICAL PEARL Long-term follow-up is where a treatment strategy proves its true value. Unlike early response signals, PEACE-1 provides mature evidence that upfront systemic intensification can translate into substantially longer survival. 💡 In appropriately selected patients with de novo mCSPC who are candidates for docetaxel, these findings strongly reinforce the role of upfront triplet therapy. The clinical question is increasingly not simply whether to intensify, but which patients should receive a triplet, how best to integrate local treatment, and how to preserve quality of life. 🎯 Precision matters—but so does acting early when a proven survival advantage is available. 👏 Congratulations to Prof. Karim Fizazi and the entire PEACE-1 team for this important long-term contribution to prostate cancer care! @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @neerajaiims @Silke_Gillessen @EfstathiouEleni @AOmlin @declangmurphy @cdanicas @montypal @DrScottTagawa @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #ProstateCancer #mCSPC #mHSPC #GUOncology #PEACE1 #TripletTherapy

PEACE-1 at 7.7 years, de novo mCSPC: abiraterone added to ADT plus docetaxel with long term improves survival. 📈 Docetaxel population, n=710: OS HR 0.68, median 6.2 vs 4.4 years, 7-year OS 45.7% vs 30.7% 📊 OS HR was 0.75 at the 2022 analysis, so the effect grew with follow-up 🔍 86% of controls got an ARPI after progression. No long-term safety signal Fizazi's point this investigator imitated trial gives us what few industry frontline trials by following patients this long. #ESMO26 #ProstateCancer #mCSPC #GUonc

PEACE-1 long-term follow-up at #ESMO26: The sustained OS benefit reinforces the importance of early ARSI use in mHSPC. Importantly, PEACE-1 does NOT answer whether triplet therapy is superior to ADT + ARSI doublet therapy. https://t.co/syf1mf084q

#KarimFizazi with final OS analysis of #PEACE1 in met hormone sensitive prostate cancer treated w abiraterone +/- XRT, and +/- docetaxel. Important OS benefit across all subsets, median survival 6.1 yrs. @oncoalert @myESMO #ESMO26 https://t.co/GApDmrPE33

Fantastic presentation by Karim Fizazi! PEACE-1 at 7.7 years: adding abiraterone to ADT + docetaxel improved median OS to 6.2 vs 4.4 years (HR 0.68) in de novo mCSPC. Durable benefit from upfront intensification! @myESMO #ESMO26 @oncoalert https://t.co/C6GdCHh36O

PEACE-1: long-term OS benefit with the triplet (ADT+Doce+Abi) irrespective of metastatic extent. Need to move beyond volume/risk categories to choose systemic therapy #ESMO26 https://t.co/ETqtBho4lq

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

Nearly 8 years of follow-up & the triplet still delivers 💪 PEACE-1: adding abiraterone to ADT + docetaxel lifts 8-year OS from 27% to 40% in de novo mCSPC, regardless of metastatic volume. The case for intensification just got stronger 👇 @RayMcDermott1 @BertrandTOMBAL #ESMO26 #ProstateCancer #OncoAlert4Sight

🚨 ESMO26 | KEYNOTE-975: Negative! Adding pembrolizumab to definitive CRT in unresectable oesophageal cancer failed to improve EFS or demonstrate an OS benefit. 📊 EFS HR 0.97 (CPS ≥10) 📊 OS HR 0.99 (overall) ❌ No benefit, even in PD-L1–high tumors. #ESMO26 #KEYNOTE975 https://t.co/NxtPcem5Pc

#ESMO26 KEYNOTE-975 @myESMO @OncoAlert https://t.co/t9ShMXpw9L https://t.co/QekcFUWwgA

#ESMO26 ❌ KEYNOTE-975 | Phase III 👥 700 pts | Unresectable EC/GEJ 💊 Pembro + dCRT vs placebo + dCRT 🔬 PD-L1 CPS≥10: 📉 EFS: 15.2 vs 14.7 mo (HR 0.97; p=0.399) ⏳ OS: 32.2 vs 35.0 mo (HR 1.00) 📊 Overall EFS: HR 0.94 🛑 Negative trial. No EFS benefit. @OncoAlert https://t.co/ljl1meUeLI

KEYNOTE-975 phs-3 study: Pembrolizumab or placebo plus concurrent definitive chemoradiotherapy in E/GEJ cancer #ESMO26 #ESMOAmbassadors 👉 mEFS: 15.2 vs 14.7 mo 👉 mOS: 32 vs 35 mo 🧐disappointing, no benefit in all & CPS>10 pts @myESMO @ASCO https://t.co/Cj0MXoAWJB

🚨 KEYNOTE-975: NEGATIVE🚨 703 pts with unresectable esophageal/GEJ cancer Pembro + dCRT vs dCRT ❌ EFS (PD-L1 CPS≥10): 15.2 vs 14.7m (HR 0.97) ❌ OS: 32.2 vs 35.0m (HR 1.00) Study stopped after EFS endpoint not met. #ESMO26 https://t.co/e4K5rKw4s5

🚨 Another reminder that adding immunotherapy to a curative-intent backbone does not automatically improve outcomes. @OncoAlert At #ESMO26, phase III KEYNOTE-975 tested pembrolizumab + definitive chemoradiotherapy versus dCRT alone in untreated, unresectable esophageal/GEJ cancer. 📊 n=703 In PD-L1 CPS ≥10: ➡️ Median EFS: 15.2 vs 14.7 months HR 0.97 (0.77–1.23) ➡️ Median OS: 32.2 vs 35.0 months HR 1.00 (0.77–1.30) ⚠️ Grade 5 AEs: 13% vs 10% ⚠️ Treatment discontinuation due to AEs: 34% vs 27% The primary efficacy signal was negative. 🎯 Why this matters: biologic plausibility and activity in metastatic disease are not enough to assume benefit in the definitive setting. For me, KEYNOTE-975 reinforces a critical principle: treatment intensification must earn its place with meaningful outcome improvement — especially when toxicity and treatment burden increase. Important data from @MDmanishshah @BennounaJaafar @cbcbc1971 and the KEYNOTE-975 investigators. Pinging @CathyEngMD @BenWestphalen @graokane @NiuSanford @GillSharlene @pashtoonkasi @DrVilmaPBarcia @GIMedOnc @DaisukeKotani @KoheiShitara #OncoAlert #ESMO26 #GICancer #EsophagealCancer #GEJCancer #Immunotherapy #Chemoradiotherapy

I’m in Madrid, and #ESMO26 is underway! Today’s watchlist, Madrid time: opening at 11:30, ESMO-MCBS and KEYNOTE-975 at 13:30, mRNA vaccines at 15:15. INTerpath-001 is tomorrow. Which result will truly change practice? I’ll report from the congress. What are you watching? https://t.co/wzhxRhmqZ9

KEYNOTE-975: adding pembro to definitive CRT didn't improve EFS in CPS>=10 esophageal/GEJ cancer. HR 0.97 (95% CI 0.77-1.23). Hierarchy stopped there; OS wasn't formally tested. Another reason not to assume IO helps every CRT backbone. #ESMO26 #radonc https://t.co/JCWWmcCZHS https://t.co/SCdkZqxsjS

🤩 @OncBrothers highlighting 🔑 studies presented on Day 1 of #ESMO26 #BreastCancer 1. #NATALEE 2. #HorizonBreast06 3. #TALENT #GIOnc 4. #RASolute302 5. #HerizonGEA01 #GUOnc 6. #KN866 7. #PEACE1 #OncTwitter #MedTwitter #bcsm #gism #gucsm @myESMO #MedX #MedEd #Oncology https://t.co/s1p1cmrz2k

NATALEE, NSABP B-42, PANKU-Breast01, TALENT, HERIZON-GEA-01, KEYNOTE-866 ve RASolute-302. Sağkalım faydası nerede gösterildi? Hangi çalışma primer sonlanımını karşılayamadı? Yeni verileri hasta grubu ve tedavi bağlamıyla birlikte değerlendirdik. #ESMO2026 https://t.co/gsMeDN50vu

Day 1 #ESMO26 highlights Breast Ca 1. #NATALEE (update): Ribo Adj HR+ 2. #HorizonBreast06: ADCs in mBC 3. #TALENT: NeoAdj TDXd HR+ GI 4. #RASolute302: Panc Ca 5. #HerizonGEA01: GEJ/Gastric GU 6. #KN866: NeoAdj Pembro MIBC 7. #PEACE1: Abi in mHSPC #OncTwitter @myESMO 1/8 https://t.co/pkQxyvyRrG

Nice update of the RASolute 302 at #ESMO26 Looking at the outcomes. Although small numbers, are we facing a roadblock with the KRAS G12R variant? Represents between 12-15% Could protein degraders be a viable alternative? #ESMOAmbassadors @myESMO @GrupoTTD https://t.co/bKh7kUhKzk

#LBA82 subgroup analysis RASolute 302 #PDAC ➡️HR for OS across subtypes 0.32-0.46 ➡️G12R 0.61 (0.29-1.30) ➡️RAS WT numbers small (3%) but still OS benefit! 🤔perhaps ORR and mPFS not as pronounced in these populations! ✅std second line treatment @myESMO #ESMO26 @OncoAlert https://t.co/J43sTtOscN

#ESMO26 🚀 RASolute 302 | Phase III 👥 500 pts | Previously treated mPDAC 💊 Daraxonrasib (RAS(ON) inhibitor) vs chemo 📈 OS: 13.2 vs 6.7 mo (HR 0.40) 🧬 OS benefit by RAS genotype: 🔹 G12D: HR 0.49 🔹 G12V: HR 0.32 🔹 G12R: HR 0.61 📊 PFS: HR 0.55 (BICR) 🎯 ORR: 32% vs 11% 💡 new SOC! @OncoAlert

Zev Wainberg presents subgroup analyses from phase 3 RASolute 302 study of #daraxonrasib in patients with previously treated metastatic #PDAC at #ESMO26 (part 2) #ESMOAmbassadors @myESMO https://t.co/xcWXBT3xw0

RASolute 302 ph3 study: Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated mPDAC #ESMO26 #ESMOAmbassadors 👉 mOS: 13.2 vs 6.7 mo 👉ORR improved in all RAS mutations 👉PFS & OS: small subgroups, favourable for all 🧐great data, consistent benefits for all pts @myESMO @ASCO

🚀Upper GI oral abstracts #ESMO26 Day 1 summary results 1) Arcotatug tavatecan improved PFS in CLDN18.2+ G/GEJA in the 3L+ setting 2) SANO trial, OS at 5 years similar between active surveillance and surgery in patients with oesophageal cancer and a complete clinical response after nCR, despite more distant metastasis 3) Adding pembrolizumab to dCRT did not improve EFS in untreated unresectable esophageal or GEJ cancer with PD-L1 CPS ≥10 4) Daraxonrasib demonstrated consistent OS benefit in different RAS mutatin subgroups in RASolute-302 5) mKRAS-specific lymph node targeted amphiphile immunotherapy in PDAC did not met primary DFS endpoint. 6) Zani + CT +/- tisle keep OS benefit in at IA2 of HERIZON-GEA-01 7) Anbenitamab plus ChT improved OS in patients with HER2-positive GC/GEJC adenoca after previous trastuzumab 8) TQB2102 (HER2 bispecific antibody-drug conjugate) plus bemotrizumab and capecitabine demonstrates promising antitumor activity in 1L of advanced GC/GEJC 9) Dostarlimab in Pts with localized dMMR/MSI-H GEA led to a 62.5% 1y-cCR at the first interim analysis, enabling organ preservation. 10) FOLFIRI and Ram vs paclitaxel in taxan-pretreated GEA imporved PFS but no OS 11) Stage II–IIIB gastric cancer after D2 resection, four months of adjuvant XELOX was noninferior to six months for 3-year DFS 12) Adding durvalumab to dCRT in locally advanced esophagus carcinoma did not improve PFS 13) Adding SBRT to MFOLFIRINOX in high risk, borderline resectable or locally advanced pancreatic cancer mproved LRR and PFS 14) FGFR2b expressing GC/GEJ with co-existing FGFR2 amp may define a biologically distinct subset with potential sensitivity to bemarituzumab #cancer #oncology #MedX #GI #gastrointestinal @OncoAlert

🚨 RASolute 302 | ESMO 2026 | LBA82 ONE DRUG. MULTIPLE RAS MUTATIONS. NEARLY DOUBLE THE SURVIVAL. Phase III | N = 500 | Previously treated metastatic pancreatic cancer. 💊 Daraxonrasib vs Chemotherapy • Median OS: 13.2 vs 6.7 months | HR 0.40 • Median PFS: 7.2 vs 3.6 months | HR 0.49 • 60% lower hazard of death 🧬 Does the RAS mutation matter? G12D → HR 0.49 G12V → HR 0.32 G12R → HR 0.61 Q61 → HR 0.37 Directionally favourable OS across RAS subgroups, although smaller subgroups remain inconclusive. TAKE-HOME Daraxonrasib could redefine treatment of previously treated metastatic pancreatic cancer. The breakthrough is broad RAS inhibition, not superiority in any individual mutation. ⚠️ Median follow-up: 8.5 months. Longer-term data remain important. 📖 Reference: Wainberg ZA et al. RASolute 302, Phase III subgroup analysis. ESMO 2026, LBA82. NCT06625320. #MVOnco #ESMO2026 #PancreaticCancer #Daraxonrasib #RAS

🚨 ESMO 2026 | RASolute 302 (LBA82) Phase III: Daraxonrasib (RAS-ON inhibitor) vs chemotherapy in previously treated mPDAC (N=500). 🔹 Median OS: 13.2 vs 6.7 months (HR 0.40) 🔹 Median PFS: 7.2 vs 3.6 months (HR 0.49) OS benefit by RAS mutation: • G12D: HR 0.49 • G12V: HR 0.32 • G12R: HR 0.61 • Q61: HR 0.37 • No RAS mutation identified: HR 0.43 A remarkable 60% reduction in the hazard of death overall, with consistent directional benefit across RAS subgroups. @myESMO @OncoAlert @OncBrothers #ESMO26 #PancreaticCancer #RAS

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

From presenting Phase 1 data at #ESMOGI24 → @NatureMedicine publication in 2025 → seeing positive Phase 3 results from G-HOPE-001 in CLDN18.2 positive 3L+ G/GEJA presented by @KoheiShitara at #ESMO26! Wonderful to have been part of the development journey of arcotatug tavatecan (IBI343), a CLDN18.2-targeting ADC! 📊 OS HR 0.57 (10.2 vs 6.9 mo) 📊 PFS HR 0.45 (7.1 vs 3.1 mo) 💊 Grade ≥3 treatment-related AEs: 47.4% vs 55.9%; dose reductions: 17.8% vs 35.1% compared with chemotherapy. Congratulations to all investigators and the Innovent & Takeda teams! Looking forward to exploring rational combinations to further improve patient outcomes! #ADC #GastricCancer @myESMO @OncoAlert @oncodaily

🚨 ESMO26 | G-HOPE-001 Arcotatug tavatecan vs chemotherapy in CLDN18.2-high advanced gastric/GEJ cancer (3L+): ✅ PFS: HR 0.47 ✅ OS: 10.2 vs 6.9 months (HR 0.57) 🎯 Promising new option for heavily pretreated patients! #ESMO26 #GastricCancer #ADC https://t.co/UuKbAFCMZu

G-HOPE-001 🇨🇳 & 🇯🇵 randomised 408 pts in the 3L+ CLDN18.2+ve G/GOJ setting!! 81% Gastric primary & 44% prev resected primary. ORR 37% vs 8% (IA2). PFS at IA1 5 vs 2 mo, HR 0.47. Toxicity seems similar to alternative tx. Impressive collaboration. #ESMO26 @OncoAlert @myESMO https://t.co/F7H6yXS2K2

#ESMO26 🧬 G-HOPE-001 | Phase III 👥 460 pts | CLDN18.2+ G/GEJA, ≥3L 💊 Arcotatug tavatecan (ADC) vs TPC 📈 PFS: 7.1 vs 3.1 mo (HR 0.45; updated) ⏳ OS: 10.2 vs 6.9 mo (HR 0.57; p<0.0001) 🎯 ORR: 37.4% vs 7.7% 🚀 Significant PFS & OS benefit! @OncoAlert https://t.co/hVpdupeq2c

G-HOPE-001 phs-3: Arcotatug tavatecan vs TPC in previously treated G/GEJA: First interim analysis #ESMO26 #ESMOAmbassadors 🇨🇳🇯🇵, 2600 prescreened, 430 included 👉ORR: 37 vs 7.7% 👉 mPFS: 7.1 vs 3.1 mo 👉 mOS: 10.2 vs 6.9 mo 🧐CLDN-2 ADC, strong signal of efficacy, acceptable safety @myESMO @ASCO

#ESMO26 | LBA77 G-HOPE-001: Ph3 Arcotatug tavatecan (CLDN-ADC) vs SoC in 3L+ CLDN18.2+ GEA ▪️PFS: 5.5 vs 2.9 mo, HR 0.47, p<0.0001 ▪️OS: 9.9 vs 7.4 mo, HR 0.63 ▪️ORR: 23.6% vs 5.3% @myESMO @OncoAlert https://t.co/3vmQypuEip

G-HOPE-001 | ESMO 2026 | LBA77 SAME TARGET. NEW WEAPON. 🎯 Can a CLDN18.2-targeted ADC outperform chemotherapy in heavily pretreated gastric/GEJ cancer? Arcotatug tavatecan (IBI343) vs chemotherapy | Phase III | N=408 🔹 PFS: 5.5 vs 2.9 months (HR 0.47) 🔹 ORR: 23.6% vs 5.3% 🔹 OS: 9.9 vs 7.4 months (HR 0.63; immature) 🔹 Grade ≥3 TEAEs: 45.8% vs 57.9% 🔹 ILD: No cases observed. TAKE-HOME A 53% reduction in progression/death hazard with a favourable safety signal. But mature OS and efficacy after prior zolbetuximab remain key unanswered questions. Ref: Shitara K et al. G-HOPE-001. ESMO 2026; LBA77. #MVOnco #ESMO2026 #GastricCancer #CLDN182 #ADC

🚨 ESMO 2026 | G-HOPE-001 (LBA77) Impressive phase III results for arcotatug tavat ecan (IBI343), a CLDN18.2-targeted ADC, in heavily pretreated advanced gastric/GEJ cancer. IBI343 vs physician's choice chemotherapy (N=408) 🔹 mPFS: 5.5 vs 2.9 months (HR 0.47; p<0.0001) 🔹 mOS: 9.9 vs 7.4 months (HR 0.63; immature) 🔹 ORR: 23.6% vs 5.3% 🔹 Grade ≥3 AEs: 45.8% vs 57.9% 🔹 ILD: 0% @KoheiShitara @myESMO @OncoAlert #ESMO26 #GastricCancer #ADC

🎬 #Podium2Screen from #ESMO26 @OncoAlert One of the most interesting things about the evERA biomarker analysis is that the treatment signal seems to hold across very different molecular contexts. @stolaney1 🇺🇸 from @DanaFarber walks us through the data: 🔹 Giredestrant + everolimus maintained PFS benefit regardless of ctDNA fraction 🔹 Benefit persisted across ESR1 variants, including Y537 🔹 The signal was also preserved in poor-prognosis subgroups such as TP53, GATA3 and RB1 🎯 Why this matters: biomarkers can tell us who has more aggressive biology — but that does not always mean they identify who will or will not benefit from a given treatment. For me, the key question is whether future analyses can move beyond prognostic stratification and identify a truly predictive signature for endocrine-based combinations after CDK4/6 inhibition. Excellent discussion by @stolaney1. @elmayermd @GregoryAVidal @jhaveri_komal @breastoncdoc @DrWGradishar @NaokiNiikura @FavretMD @DraAlfie @hoperugo @BianchiniGP #OncoAlert #BreastCancer #ESR1 #ctDNA #PrecisionOncology #EndocrineTherapy

🎬 New @OncoAlert #Podium2Screen from #ESMO26 🇪🇸 Our #BreastCancer faculty member @stolaney1 🇺🇸(@DanaFarber) walks us through her #ESMO26 presentation: biomarker analyses from evERA https://t.co/xCULUhGm3B

From the podium to your screen!! Before the applause is even over! @OncoAlert #Podium2Screen brings @stolaney1’s #ESMO26 evERA biomarker data straight to the feed: giredestrant + everolimus maintained benefit across ctDNA burden, ESR1 variants and poor-prognosis subgroups. At ESMO, the data move fast. OncoAlert moves faster 😏 @_SEOM @myESMO

🎬 New @OncoAlert 🚨 #Podium2Screen from #ESMO26 🇪🇸 @stolaney1 discusses #evERA biomarker analyses: giredestrant + everolimus maintained its PFS benefit across ctDNA fractions, ESR1 variants and poor-prognosis subgroups with TP53, GATA3 or RB1 alterations. #BreastCancer https://t.co/uoaZFwjHzt

🔥 In ESR1mut mBC, giredestrant + everolimus (evERA) shows benefit across biomarker subgroups (TP53mut, PIK3CAmut, RB, ctDNA fraction) Key data to navigate the complex post-CDK4/6i landscape ‼️Unmet need ➡️ Head-to-head trials in biomarker-overlapping populations #ESMO26 https://t.co/Xar03heoQC

Bill Gradishar also opens a thoughtful cross trial comparison as discussing EvERA. #ESMO26 @OncoAlert https://t.co/XhD7BDlhyC

evERA BC exploratory biomarker analysis @stolaney1 Giredestrant + everolimus showed PFS benefit vs standard ET + everolimus across ctDNA tumour fractions and ESR1 mutation variants, including Y537 and D538, regardless of clonality. Encouraging consistency despite ESR1 heterogeneity; smaller genomic subgroups remain exploratory. #BCSM #ESMO26 @OncoAlert @Larvol

evERA BC (Exploratory Analysis) #ESMO26 @stolaney1 Giredestrant + everolimus improved PFS vs standard ET + everolimus in HR+/HER2− advanced breast cancer (HR 0.56; ESR1m: HR 0.38). Benefit was generally consistent across ESR1 variants, clonality, and poor-prognosis genomic subgroups.

At #ESMO26 rapid oral session, @stolaney1 presents biomarker analysis of evERA Benefit of giredestrant + everolimus consistent across all analysed subgroups @OncoAlert https://t.co/pMDpNKb3ZM

#ESMO26 | evERA – Biomarker Analysis In the post-CDK4/6 setting, the PFS benefit of giredestrant + everolimus was maintained in patients with single and multiple ESR1 mutations (HR 0.38 and 0.48), and across clonal and subclonal variants. High ctDNA tumour fraction was associated with poorer prognosis, but benefit remained evident: PFS 7.4 vs 4.6 months; HR 0.52. Encouraging results despite biological heterogeneity. However, uncertainty in small subgroups means these exploratory findings are not yet sufficient to guide variant-specific treatment selection.

Am I the only one at #ESMO26 who thinks FOURLIGHT-1 lacks an appropriate comparator? Why not use everolimus plus endocrine therapy (investigator’s choice) as the control arm, as in evERA? #ESMOAmbassadors @myESMO https://t.co/pAOS02wRcT

Combining SG, EV and ZIM achieved an 83% ORR, including 3 complete responses, in previously untreated metastatic urothelial cancer. Watch @RandySweis discuss TROPHY-U-01 trial👉 https://t.co/vG2NVS8Gs3 #ESMO26

#ESMO26 Can two ADCs + IO push response rates even higher in 1L metastatic urothelial cancer? 🚨TROPHY-U-01 Cohort 7, evaluating sacituzumab govitecan + enfortumab vedotin + zimberelimab (N=21). 🔹 ORR 81%, including 14% CR 🔹 Median DOR 16.7 months 🔹 Median PFS 19.3 months 🔹 Median OS not reached 🔹 Grade ≥3 treatment-related AEs: 52%; 33% discontinued ≥1 agent Impressive early activity from dual ADC targeting Trop-2 + Nectin-4, but the key question is whether the added efficacy justifies the toxicity over EV+pembrolizumab. @UroToday @myESMO

🚨⭐🟠 #ESMO26 | GU Oncology — Invited Discussion KEYNOTE-866 • ENERGIZE • TROPHY-U-01 🎤 Prof. Robert Jones 🇬🇧 @OncoAlert @urologysummit 🔬 Why do apparently similar trials produce different outcomes? An excellent critical appraisal of perioperative immunotherapy in #MIBC and emerging triplet strategies in metastatic #UrothelialCancer. 📊 1️⃣ PERIOPERATIVE IMMUNOTHERAPY ✅ NIAGARA: EFS HR 0.68 ❌ KEYNOTE-866: EFS HR 0.88 ❌ ENERGIZE: EFS HR 0.94 But are these trials directly comparable? 📌 Important baseline differences: • T2 disease: 40% vs 15% vs 76% • 24-month control-arm EFS: 59.8% vs 70% vs 71.6% Different populations, endpoints and statistical designs complicate cross-trial interpretation. 🧬 2️⃣ ctDNA: PROGNOSTIC ≠ PREDICTIVE Pretreatment ctDNA positivity was associated with shorter EFS and OS. ⚠️ In ENERGIZE, baseline ctDNA positivity differed between arms (59% vs 51%), potentially introducing prognostic imbalance. 🔬 ctDNA clearance before cystectomy identified patients with more favorable outcomes. But can ctDNA clearance identify candidates for bladder preservation? Not yet! Prospective validation is essential before considering omission of radical cystectomy. 💊 3️⃣ DUAL ADC + IMMUNOTHERAPY: THE NEXT FRONTIER? TROPHY-U-01 Cohort 7: ✅ ORR 81% ✅ Median PFS 19.3 months ✅ Median DoR 16.7 months ⚠️ Grade ≥3 treatment-related AEs: 52% ⚠️ Treatment-related discontinuation of ≥1 agent: 33% Promising efficacy, but only 21 patients and no randomized comparator. ⭐ MY POINT OF VIEW CLINICAL PEARLS 🔹 A positive trial does not prove the superiority of one checkpoint inhibitor over another. 🔹 ctDNA may redefine risk stratification, but molecular clearance is not yet a license to omit surgery. 🔹 Dual ADC intensification is scientifically exciting, but added efficacy must justify added toxicity. 💡 The future of GU oncology is not about treating everyone more aggressively. It is about treating the right patient with the right strategy, at the right time. 📌 PRACTICE IMPLICATION These new results do not independently establish a new standard of care. Individual trials must be interpreted on their own merits. Access also matters: perioperative gemcitabine/cisplatin + durvalumab remains an important option where EV + pembrolizumab is unavailable. 🌍 GU Oncology Community @gbanna74 @ravikanesvaran @urologysummit @tompowles1 @PGrivasMDPhD @apolo_andrea @sonpavde @DrYukselUrun @yekeduz_emre @drenriquegrande @TiansterZhang @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #GUOncology #ctDNA #OncoAlert

🎯 #ESMO26 moving to advanced UC the TROPHY-U-01 Cohort 7: Study show Excellent ORR (81%) and mPFS 19.3 mo of the Sacituzumab + EV + Zimbe !😊 @OncoAlert @myESMO @urotoday @PGrivasMDPhD @DrChoueiri https://t.co/r7dqmqRjAh

Triple therapy signal by @RandySweis in TROPHY-U-01 Cohort 7 Ph.Ib: SG + EV + zimberelimab in untreated metastatic UC. ORR 83%, including 3 CRs (n=18 evaluable). Grade ≥3 TEAEs 62%; discontinuation 33%. Promising activity, however toxicity and small sample warrant caution. #ESMO26 #BladderCancer @myESMO @OncoAlert

TROPHY-U-01 Cohort 7: SG + EV + zimberelimab demonstrated promising efficacy (ORR 81%, n=21). Looking forward to results from larger phase II/III trials! #ESMO26 https://t.co/1Q5SfsTaVA

Is it time for triplets in frontline la/mUC? Really enjoyed hearing Randy Sweis present SG + EV + zimberelimab in TROPHY-U-01 Cohort 7. Impressive ORR of 81%, median PFS 19.3 mo (n=21). Promising early data, but larger studies needed to assess added benefit and toxicity. #ESMO26 @OncoAlert

TROPHY-U-01 Cohort 7: SG + EV + Zim in 1L mUC. Any role for triplets in the near future? Hard to compete against EVP. #ESMO26 https://t.co/GMz7qg29IO

#ESMO26 | TROPHY-U-01 Cohort 7: Sacituzumab govitecan + EV + zimberelimab in advanced urothelial cancer. Promising early activity: ORR 81%, median PFS 19.3 months, and OS not reached. @SCUColombia @achoHematoYOnco @myESMO @ASCO @OncoAlert @oncodaily https://t.co/cf8p8r418j

#ESMO26 Day 1 has arrived! Follow along with @OncoAlert for full coverage! Highlights from the GU Renal & Urothelial Proffered Paper Session today: 🔴 Ph 3 KEYNOTE-866 (GC +/- perioperative pembro in MIBC) 🔴 Ph 3 ENERGIZE (GC +/- perioperative nivo in MIBC) 🔴 Ph 1 TROPHYU-01 Cohort 7 (SG + EV + Zim in 1L La/mUC) 🔴 ctDNA analyses from Ph 3 KEYNOTE-B15 (EV+P vs GC in cis-eligible MIBC) Key❓: Why were KN-866 and ENERGIZE negative while NIAGARA was positive? @scocmem @nataliagandur @DrKarineTawagi @niklas_kluemper @OncoAlert

Long-term #GIM3FATA data at #ESMO26 🇪🇸 : no DFS or OS difference between upfront AI and tamoxifen followed by AI Exemestane showed worse DFS than anastrozole, with a 4.9% absolute difference at 10 years, but no OS difference. Presented by @PietroDePlacido 👏 @OncoAlert #BreastCancer

Ok, #bcsm, what do we make of exemestane looking worse than anastrazole by 4.9% in GIM3 FATA? Fluke? Otherwise, no difference between upfront or switch strategies. #ESMO26 #ESMOAmbassadors https://t.co/noFZyCgacr

Interesting signal emerging from the long-term analysis of GIM3 FATA, presented by @PietroDePlacido: exemestane was associated with a slightly worse 10-year DFS (but similar OS) compared with non-steroidal AIs. Important to look at the type of events. #ESMO26 #ESMOAmbassadors https://t.co/kju0SET6xp

In a 2x2 factorial design, GIM3 FATA shows no difference by schedule , and inferiority of exemestane. Important long-term data. @OncoAlert #ESMO26 https://t.co/5924e0UYSo

GIM3 FATA presented by @PietroDePlacido Upfront AI and switching from tam showed no difference in DFS or OS Exemestane had a slightly worse DFS than anastrozole, no difference in OS @OncoAlert #ESMO26 https://t.co/hge3aYreRS

🌸 Sometimes mature follow-up simplifies the question rather than complicating it. @OncoAlert At #ESMO26, the final analysis of the GIM3 FATA trial revisits two practical issues in postmenopausal HR+ early #BreastCancer: 1️⃣ Is upfront AI better than switching after tamoxifen? 2️⃣ Are all aromatase inhibitors equivalent? 📊 n=3,697 ➡️ Upfront vs switch: DFS HR 0.95 OS HR 0.88 → no clear schedule advantage ➡️ 10-year DFS: Anastrozole 79.1% Letrozole 76.6% Exemestane 74.2% ➡️ Exemestane vs anastrozole: adjusted DFS HR 1.23 ➡️ 10-year OS: no significant difference across AIs 🎯 Why this matters: there was no winning schedule, and long-term outcomes reinforce that endocrine therapy should remain highly individualized. For me, the practical message is simple: when efficacy differences are modest, tolerability, comorbidities, adherence, bone health, and cost become part of the treatment decision — not secondary considerations. Important mature data from @PietroDePlacido @antoniorusso_pa @delmastro_lucia @MicheleDelauren @fperrone62 and the FATA investigators. Pinging @matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @hoperugo @stolaney1 @BianchiniGP @kevinpunie @ElisaAgostinett #OncoAlert #ESMO26 #BreastCancer #EndocrineTherapy #AromataseInhibitors #Survivorship

Exciting phase 3 trials data in metastatic #ProstateCancer @myESMO #ESMO26 #ESMOAmbassadors #PEACE1 #Capitello281 @Silke_Gillessen @neerajaiims @OncoAlert @OncBrothers @PCFnews @shilpaonc @EAntonarakis @Parminder1699 @Uromigos @montypal @docjavip @drenriquegrande @cdanicas https://t.co/epveHRbSgb

From biology to patient benefit. CAPItello-281 brings PTEN-targeted therapy closer to clinical reality. Proud to contribute to this research. @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 @Annals_Oncology @tompowles1 https://t.co/sjbr090iIL

#ESMO26 | CAPItello-281 update: Capivasertib + abiraterone improves OS in PTEN-deficient mHSPC (HR 0.82; 57.4 vs 46.5 months), with sustained rPFS benefit. A promising first-line strategy! @SCUColombia @achoHematoYOnco @myESMO @ASCO @OncoAlert @oncodaily#ProstateCancer https://t.co/G8nh5VAzjn

Updated CAPItello-281 data at #ESMO26 In PTEN-deficient mHSPC, capivasertib + abiraterone improved median OS (57.4 vs 46.5 months; HR 0.82) and rPFS (35.5 vs 26.0 months). Encouraging OS trend, but not statistically significant at this analysis #KarimFizazi @OncoAlert https://t.co/xvPGYUnGkL

🚨 #ESMO26 GU Oncology — the studies I would keep closest on the radar @OncoAlert What stands out from the @OncoAlert GU selection is how clearly the field is moving toward perioperative intensification, biomarker-driven treatment, smarter sequencing, and new mechanisms of action. 🟠 #BladderCancer VOLGA · KEYNOTE-B15 · ENERGIZE · KEYNOTE-866 🔵 #ProstateCancer DASL-HiCaP · CAPItello-281 · PROTEUS 🟢 #KidneyCancer LITESPARK-011 · LITESPARK-012 · ivonescimab · PE-PE · SWOG S2200 · XmAb819 🎯 Why this matters: these are not just isolated trial readouts. Together, they are redefining where we intensify, where we de-escalate, how we select patients, and how earlier disease settings are becoming increasingly systemic and biology-driven. For me, the most important question across all three tumors is the same: Who actually needs more treatment — and who can safely receive less? That is where GU oncology is heading. Proud to be part of this @OncoAlert faculty following the data closely at #ESMO26. @DrChoueiri @tompowles1 @neerajaiims @PGrivasMDPhD @TiansterZhang @AndreaNecchi @DrRanaMcKay @DrYukselUrun @crisbergerot @nataliagandur #OncoAlert #GUOncology #PrecisionOncology #CancerResearch

Lovely walking tour & sunset in Madrid @myESMO #ESMO26 Looking forward today to: #VOLGA peri-op durva/treme/EV MIBC & Daro in very high risk PCa both in presidential session🌟 #KNB15 ctDNA analysis Claudin-6 ADC in GCT #CAPITELLO281 capi OS in mCSPC NAT ICI in penile CA https://t.co/p31vBubCOj

🚨 #ESMO26 Lung Cancer: the 10 studies that best capture where the field is moving @OncoAlert What stands out to me from the @OncoAlert faculty selection is how much the lung cancer landscape is shifting toward smarter sequencing, biomarker-defined combinations, and more selective treatment intensification. 🫁 Top Ten from Madrid: 1️⃣ DeLLphi-305 — tarlatamab + durvalumab in 1L ES-SCLC maintenance 2️⃣ Krascendo 1 — divarasib vs sotorasib/adagrasib in KRAS G12C NSCLC 3️⃣ SAFFRON — osimertinib + savolitinib after osimertinib in EGFRm/MET+ disease 4️⃣ OptiTROP-Lung04 — sac-TMT after EGFR-TKI 5️⃣ OptiTROP-Lung06 — sac-TMT + pembrolizumab in PD-L1-negative NSCLC 6️⃣ PERSEE — pembrolizumab ± chemotherapy in PD-L1 ≥50% 7️⃣ SANOVO — savolitinib + osimertinib in 1L EGFRm/MET-overexpressed NSCLC 8️⃣ IFCT-2103 DIAL — continue pembrolizumab vs observation at 6 months 9️⃣ PANKU-Lung01 — iza-bren after third-generation EGFR TKI 🔟 SARON — consolidation RT in oligometastatic NSCLC 🎯 Why this matters: these studies are not just adding new drugs. They are refining when to intensify, when to combine, when to continue, and when biology should drive the next step. That is the real value of a “Top Ten” list: not more information — better prioritization of the data most likely to influence practice. @christine_lovly @GlopesMd @DrSanjayPopat @StephenVLiu @jillfeldman4 @UOzkerim @DrMirallas @CharuAggarwalMD @peters_solange @JordiRemon #lcsm #OncoAlert #ESMO26 #LungCancer #NSCLC #SCLC #PrecisionOncology

SAFFRON trial ESMO 2026 Osimertinib plus savolitinib after osimertinib resistance in EGFR-mutant NSCLC Phase III trial First Glimpse https://t.co/rAnhPyNkhM

@myESMO @LungCancerRx @OncoAlert @oncodaily 2/ SAFFRON (LBA6), Oct 25, 16:54 CET Osimertinib + savolitinib vs platinum–pemetrexed, EGFRm MET-high NSCLC after osimertinib. Sponsors report PFS + OS wins. How big, and which MET IHC/FISH cutoff selects patients? @LungCancerRx @OncoAlert @oncodaily https://t.co/a1jM7oyRXW

Please join us on Sunday for novel first-line phase 3 data of #ivonescimab in advanced #BTC #CCA #biliary tract cancer at #ESMO26 #ESMOAmbassadors #Presidential Symposium II @myESMO https://t.co/xeb8KRqksk

🦉 Cancer Immunotherapy: A Week of Breakthroughs, Setbacks and New Biological Insights October 17–24, 2026 This week brought two major clinical advances: a personalized mRNA cancer vaccine significantly reduced melanoma recurrence, while a T-cell engager sharply extended survival in aggressive lung cancer. Other studies revealed why CAR-T cell quality, antigen presentation, and the tumor microenvironment can matter as much as immune activation itself. 🩸 1. A Personalized Cancer Vaccine Passes Its Biggest Test Moderna and Merck's individualized mRNA vaccine, intismeran autogene, reduced melanoma recurrence or death by 42% when combined with pembrolizumab in the Phase 3 INTerpath-001 trial. Among 1,137 patients with resected stage IIB–IV melanoma, two-year recurrence-free survival reached 82.2% versus 70.0% with pembrolizumab alone. Distant metastasis or death risk fell 38%, without a substantial increase in severe treatment-related toxicity. The results provide major randomized evidence that vaccines targeting patient-specific tumor mutations can improve clinical outcomes, not merely generate immune responses. Overall-survival data remain immature, and personalized manufacturing presents practical challenges. Source: https://t.co/FHlL1f9wPs 🩸 2. T-Cell Engagers Nearly Double Survival in Lung Cancer The Phase 3 DeLLphi-305 trial showed that adding Amgen's DLL3-targeted T-cell engager tarlatamab to durvalumab maintenance therapy extended median survival from 12.7 to 21.1 months in extensive-stage small-cell lung cancer. Among 563 patients, the combination reduced mortality risk by 58% and increased progression-free survival from 1.9 to 7.4 months. Tarlatamab recruits T cells directly to cancer cells, complementing durvalumab's PD-L1 blockade. The survival advantage is substantial, but cytokine-release syndrome occurred in 49.6% of patients, predominantly grade 1–2. Grade ≥3 treatment-related adverse events affected 20.9% versus 10.8%. These results could reshape first-line maintenance treatment, subject to regulatory review. Source: https://t.co/1TRq9VtseZ 🩸 3. Bladder Cancer Treatment Takes a Major Step Forward The Phase 3 VOLGA trial demonstrated a significant survival advantage with enfortumab vedotin plus durvalumab in patients with muscle-invasive bladder cancer unable or unwilling to receive cisplatin. Among 462 patients, the combination reduced the risk of progression, recurrence or death-related events by 49%. Two-year event-free survival reached 64% versus 45%, while overall survival was 78% versus 69%. The strategy combines targeted cytotoxic delivery through an antibody–drug conjugate with PD-L1 checkpoint inhibition. However, grade 3–4 adverse events occurred in 64% versus 44%. The results support a new perioperative option, although comparisons with other modern regimens remain unavailable. Source: https://t.co/VLXeYEzs9O 🩸 4. CAR-T Quality May Matter More Than Expansion A multicenter study involving 783 lymphoma patients found that CAR-T products enriched in naïve-like CCR7⁺CD45RA⁺ T cells were associated with significantly longer progression-free survival. In the primary cohort of 580 patients receiving axi-cel, these cells predicted better outcomes (HR 0.46; p=9.8×10⁻⁵), independently of tumor burden, inflammation and CAR-T expansion. An additional 203 patients confirmed the association. More previous treatment lines were linked to fewer naïve-like cells. The implication challenges a familiar assumption: expanding more CAR-T cells may be less important than preserving cells capable of sustained antitumor activity. Whether manufacturing changes that enrich these populations actually improve survival remains unproven. Source: https://t.co/GAN67wP3OV 🩸 5. A New Approach to Severe Immunotherapy Toxicity Researchers in Germany and Switzerland reported promising results using extracorporeal photopheresis to treat severe immune-related complications resistant to corticosteroids. The technique treats collected immune cells with a photosensitizing agent and ultraviolet light before returning them to circulation. In a prospective Phase 1b/2 study involving 30 patients, the response rate among evaluable inflammatory complications reached 96.3%, including responses in colitis, hepatitis and dermatitis. Treatment reduced inflammatory T-cell activity, including granzyme expression and interferon-γ/TNF signaling. No treatment-related serious adverse events occurred. The potential advantage is controlling dangerous inflammation without escalating systemic immunosuppression. However, the uncontrolled study cannot establish comparative efficacy or confirm preservation of antitumor immunity. Source: https://t.co/xDE6iBNXhy 🩸 6. Selective T-Cell Activation Shows Activity in Resistant Tumors Invikafusp alfa, an experimental bispecific antibody, activates selected T-cell populations expressing Vβ6 or Vβ10 T-cell receptors rather than broadly stimulating the immune system. In the Phase 1/2 START-001 trial, 4 of 27 patients (14.8%) treated at biologically optimal doses achieved objective responses, while 59.3% experienced disease control. Responses included microsatellite-stable colorectal cancer and PD-L1-negative lung cancer, where conventional checkpoint inhibition often has limited efficacy. The treatment expanded memory-like target T cells without broadly activating unrelated populations. This demonstrates preliminary clinical activity, not established benefit. Patient numbers remain small, durability is uncertain, and cytokine-release syndrome remains a risk. Source: https://t.co/2KupIGrKnT 🩸 7. Strong Vaccine Immunity Fails to Improve Pancreatic Cancer Outcomes The randomized Phase 2 AMPLIFY-7P trial tested camupepimut (ELI-002 7P), an off-the-shelf vaccine targeting mutant KRAS, in 144 patients with pancreatic cancer after standard treatment. Despite vaccine-specific T-cell responses in 98.9% of evaluable patients, the primary disease-free survival endpoint was missed: 23.8 versus 21.2 months (HR 0.85; p=0.5329). Subgroup analyses suggested possible benefit in patients without detectable circulating tumor DNA (HR 0.51) or prior radiotherapy (HR 0.59). The contrast is striking: nearly universal immune activation did not translate into a significant overall clinical benefit. Vaccination may work better against minimal residual disease, but subgroup signals remain exploratory and clinical efficacy is unproven. Source: https://t.co/18SHt23Nqc 🩸 8. Dual Checkpoint Blockade Targets Difficult Biliary Cancers Chinese investigators reported Phase 2 results for cadonilimab, a bispecific antibody blocking PD-1 and CTLA-4, combined with gemcitabine and cisplatin in advanced biliary tract cancer. Among 61 patients, the objective response rate reached 55.7%, with disease control in 85.2%. Median progression-free survival was 8.0 months and overall survival 15.6 months. Dual checkpoint blockade could provide broader immune activation than PD-1/PD-L1 inhibition alone. However, grade ≥3 adverse events occurred in 68.9%, including severe immune-related events in 18%. The single-arm design cannot establish superiority over approved chemoimmunotherapy. Randomized comparisons must determine whether increased immune stimulation produces a meaningful survival advantage. Source: https://t.co/aLKEXWZ2Vq 🩸 9. Tumors Can Hide Antigens Without Losing Them Researchers at Southern Medical University identified SMPD3, an enzyme involved in sphingolipid metabolism, as an unexpected regulator of tumor antigen presentation. In colorectal cancer models, increasing SMPD3 enhanced MHC-I expression at the cell surface without substantially increasing total MHC-I abundance. The mechanism involved intracellular trafficking rather than greater production of antigen-presenting proteins. SMPD3 overexpression increased CD8 T-cell infiltration, suppressed tumor growth in mice and improved experimental PD-1 blockade responses. This reveals another route to immune escape: cancer cells may retain antigen-presentation machinery but fail to deliver it to their surface. The findings are preclinical. SMPD3 is not yet a validated therapeutic target or clinical biomarker. Source: https://t.co/2J4IGGJiOI 🩸 10. Macrophages May Awaken Sleeping Cancer Cells French researchers uncovered a mechanism through which macrophages can reactivate dormant breast cancer cells. In three-dimensional tumor models, macrophage-derived MMP9 and lysyl oxidase (LOX) remodeled the surrounding extracellular matrix, activating EGFR/HER2 signaling and pushing dormant cancer cells toward renewed proliferation. Remarkably, this signaling occurred without conventional receptor-ligand activation. The finding links macrophage activity, tissue remodeling and metastatic recurrence through a mechanism distinct from classical checkpoint-mediated immune suppression. It raises the possibility that preventing relapse may require controlling the tumor's surrounding tissue environment, not just targeting residual cancer cells. The evidence comes from laboratory models. Its role in human metastatic recurrence and potential for therapeutic intervention remain unproven. Source: https://t.co/Z4TfhFEx9b

The phase II AMPLIFY-7P trial evaluated camupepimut (ELI-002 7P) in resected KRAS-mutated pancreatic cancer. Watch @EileenMOReilly discuss the trial 👉 https://t.co/Tx9kEYZFwB #ESMO26

Proffered paper on #PDAC by @EileenMOReilly at @myESMO #ESMO26 - AMPLIFY-7P Randomized phase II trial Stage II-III KRAS-mutated respected PDAC - adjuvant Camupepimut (ELI-002 7P) Phase-III ongoing based on promising prespecified DFS at 6m data #ESMOAmbassadors https://t.co/gAyooiQgVQ

AMPLIFY-7P randomised ph2 ✅7-valent(camupepimut) mKRAS lymph node targeted amphiphile ➡️curative intent & no recurrence <6mth #PDAC ✅T cell responses,primary endpt-ve ➡️benefit in ctDNA-ve& no rads? ➡️DFS @6mth benefit of 14% p=0.056 ✅ph3 planned @myESMO @OncoAlert #ESMO26 https://t.co/GROQV9n9I8

🚨 ESMO 2026 | AMPLIFY-7P KRAS vaccine camupepimut in resected PDAC: ❌ Primary DFS endpoint not met (HR 0.85; p=0.53). ✅ ctDNA−: HR 0.51 ✅ ctDNA+: HR 0.57 ✅ Strong KRAS-specific T-cell response linked to better DFS (HR 0.22). 🎯 Promising signals.. #ESMO26 https://t.co/TKRwGZxa43

EileenO’Reilly presents AMPLIFY-7P randomized phase 2 study of adjuvant camupepimut in patients with resected #KRAS-mutant #PDAC at #ESMO26 #ESMOAmbassadors @myESMO https://t.co/WAM8MlkrIs

AMPLIFY-7P ph 2 study: Seven-valent mKRAS-specific lymph node targeted amphiphile immunotherapy versus observation in resected PDAC) #ESMO26 #ESMOAmbassadors 👉 Targeting lymph nodes to activate T-cells 👉T-cells response in 99% of pts 👉poor outcome in ctDNA pos pts 🧐promising data, specifically in pts with Tcell response @myESMO

#ESMO26 💉 AMPLIFY-7P | Phase II 👥 144 pts | Resected PDAC 💊 Camupepimut (KRAS vaccine) vs observation ❌ Primary DFS endpoint not met: 23.8 vs 21.2 mo (HR 0.85; p=0.53) 🔬 Exploratory findings: 🧬 ctDNA+ predicts poor DFS (HR 6.56) 📈 No prior RT: DFS 23.8 vs 10.4 mo 💡 Signals warrant further investigation. @OncoAlert

⭐️Optimal integration and duration of pembrolizumab will be evaluated in two critical studies that I believe address very practical concerns for thoracic oncologists. 1⃣PERSEE phase 3 trial (GFPC 01-2020) - will address the value of pembrolizumab in PD-L1 ≥50% 2⃣IFCT-2103 DIAL phase 2-3 randomized trial - will address value of continuing maintenance pem/pembro beyond 2 yrs in a prospective fashion. @lcsmchat @OncoAlert @OncLive @Onco_Nexus @LungCancerEu @Lung_Cancers @LungCancerRx @MedwatchHQ @YoungLungCancer

🚨 #ESMO26 Lung Cancer: the 10 studies that best capture where the field is moving @OncoAlert What stands out to me from the @OncoAlert faculty selection is how much the lung cancer landscape is shifting toward smarter sequencing, biomarker-defined combinations, and more selective treatment intensification. 🫁 Top Ten from Madrid: 1️⃣ DeLLphi-305 — tarlatamab + durvalumab in 1L ES-SCLC maintenance 2️⃣ Krascendo 1 — divarasib vs sotorasib/adagrasib in KRAS G12C NSCLC 3️⃣ SAFFRON — osimertinib + savolitinib after osimertinib in EGFRm/MET+ disease 4️⃣ OptiTROP-Lung04 — sac-TMT after EGFR-TKI 5️⃣ OptiTROP-Lung06 — sac-TMT + pembrolizumab in PD-L1-negative NSCLC 6️⃣ PERSEE — pembrolizumab ± chemotherapy in PD-L1 ≥50% 7️⃣ SANOVO — savolitinib + osimertinib in 1L EGFRm/MET-overexpressed NSCLC 8️⃣ IFCT-2103 DIAL — continue pembrolizumab vs observation at 6 months 9️⃣ PANKU-Lung01 — iza-bren after third-generation EGFR TKI 🔟 SARON — consolidation RT in oligometastatic NSCLC 🎯 Why this matters: these studies are not just adding new drugs. They are refining when to intensify, when to combine, when to continue, and when biology should drive the next step. That is the real value of a “Top Ten” list: not more information — better prioritization of the data most likely to influence practice. @christine_lovly @GlopesMd @DrSanjayPopat @StephenVLiu @jillfeldman4 @UOzkerim @DrMirallas @CharuAggarwalMD @peters_solange @JordiRemon #lcsm #OncoAlert #ESMO26 #LungCancer #NSCLC #SCLC #PrecisionOncology

#ESMO26 🧬 COMPANION-002 | Phase III 👥 Previously treated BTC 💊 Paclitaxel + tovecimig vs paclitaxel 🎯 ORR: 18% vs 5.3% 📈 mPFS: 4.7 vs 2.6 mo ⏳ mOS: 8.9 vs 9.4 mo ❌ No OS benefit despite improved ORR & PFS. 💡 Promising activity, but not a new SoC @OncoAlert https://t.co/FmLrj0bVe1

Excited to see our COMPANION-002 trial published in JCO and presented at #ESMO26! Treatment options remain limited for advanced biliary tract cancer after first-line therapy, especially without targetable mutations. Tovecimig + paclitaxel vs paclitaxel alone: • Tumor response (ORR): 18% vs 5.3% • Time without progression (median PFS): 4.7 vs 2.6 months (HR 0.44) Proud to have contributed to this multicenter trial!

🧬 A bispecific hitting DLL4 + VEGF-A can clearly move response and PFS — but the toxicity trade-off matters. @OncoAlert @myESMO At #ESMO26, a randomized phase 2/3 trial tested tovecimig + paclitaxel versus paclitaxel alone in previously treated advanced biliary tract cancer. 📊 n=168 ➡️ ORR: 17.1% vs 5.3% p=0.031 ➡️ Median PFS: 4.7 vs 2.6 months HR 0.44, p<0.0001 ➡️ OS: HR 1.05 Interpretation limited by 54% crossover But the safety signal deserves attention: ⚠️ Grade ≥3 hypertension: 44% ⚠️ Treatment discontinuation due to TEAEs: 40% vs 15% 🎯 Why this matters: the efficacy signal is real, especially for PFS, but in a heavily pretreated population the clinical value will depend on whether we can identify patients who gain enough benefit to justify the added toxicity. For me, the next question is whether DLL4/VEGF biology can become a true selection strategy, rather than another broadly applied antiangiogenic approach. Important data from @DrElkhoueiry @JavleMilind and collaborators. Pinging @CathyEngMD @BenWestphalen @graokane @NiuSanford @GillSharlene @pashtoonkasi @DrVilmaPBarcia @GIMedOnc @DaisukeKotani @KoheiShitara #OncoAlert #ESMO26 #BiliaryTractCancer #GIOncology #Bispecifics #PrecisionOncology

A randomized trial of paclitaxel ± tovecimig in previously treated patients with advanced biliary tract cancer #ESMO26 #ESMOAmbassadors 👉 ORR: 18 vs 5.3% 👉 mPFS: 4.7 vs 2.6 mo 👉 mOS: 8.9 vs 9.4 mo 🧐Active drug, but no OS benefit in 2nd line, could be explored in 1L @myESMO @ASCO

Paclitaxel +\-tovecimig: COMPANION-002 ph2/3 ➡️prev treated #BTC wo actionable alterations ➡️ORR 17.1 v5.3%; DCR 62 v 37% ➡️mPFS 4.7 v 2.6mths - benefits seen at PFS2 noting crossover ➡️OS not sig but nb crossover @myESMO #ESMO26 @OncoAlert https://t.co/eeR74Ehqed

COMPANION-002 Proffered paper by #NiloAzard on #tovecimig (VEGFA-DLL4) + paclitaxel vs paclitaxel after prior chemo in #BiliaryMalignancies ORR 18% vs 5% PFS 4.7 vs 2.6; HR 0.4 Higher dose modification 👉Development continues @myESMO #ESMO26 #ESMOAmbassadors https://t.co/M2g5xoL3qA

Signal in previously treated biliary tract cancer at #ESMO26: Tovecimig + paclitaxel improves ORR (17% vs 5%) and PFS (HR 0.44)…but with substantial toxicity, and OS remains uninterpretable given 54% crossover 🤷🏻‍♂️ @OncoAlert 4Sight is already dissecting the abstracts worth watching! 👀 @OncoReporte @_SEOM @myESMO

🚀Day 2 #ESMO26 Upper GI oral abstracts, summary results 🟢Paclitaxel + tovecimig ( vs paclitaxel) in 2L of advanced BTC improved ORR and PFS 🟢Adjuvant GemCis vs capecitabine in BTC, DFS median 2.14 vs. 1.49 years, log-rank p=0.097 🟣STRIDE ± L + TACE (EMERALD-3), stable liver function over treatment period and comparable safety regardless of baseline liver function 🟣BGB-B2033 (GPC3 x 4-1BB bispecific antibody) monotherapy in advanced HCC (phase I): promising ORR, further development #cancer #oncology #MedX #GI #gastrointestinal #biliary #liver #hcc #cholangiocarcinoma @OncoAlert

🚨 #ESMO26 GU Oncology — the studies I would keep closest on the radar @OncoAlert What stands out from the @OncoAlert GU selection is how clearly the field is moving toward perioperative intensification, biomarker-driven treatment, smarter sequencing, and new mechanisms of action. 🟠 #BladderCancer VOLGA · KEYNOTE-B15 · ENERGIZE · KEYNOTE-866 🔵 #ProstateCancer DASL-HiCaP · CAPItello-281 · PROTEUS 🟢 #KidneyCancer LITESPARK-011 · LITESPARK-012 · ivonescimab · PE-PE · SWOG S2200 · XmAb819 🎯 Why this matters: these are not just isolated trial readouts. Together, they are redefining where we intensify, where we de-escalate, how we select patients, and how earlier disease settings are becoming increasingly systemic and biology-driven. For me, the most important question across all three tumors is the same: Who actually needs more treatment — and who can safely receive less? That is where GU oncology is heading. Proud to be part of this @OncoAlert faculty following the data closely at #ESMO26. @DrChoueiri @tompowles1 @neerajaiims @PGrivasMDPhD @TiansterZhang @AndreaNecchi @DrRanaMcKay @DrYukselUrun @crisbergerot @nataliagandur #OncoAlert #GUOncology #PrecisionOncology #CancerResearch

✈️ En route to Madrid for #ESMO26, landing just in time for the data to start Friday morning. Most excited for: VOLGA LBA2 in bladder cancer, INTerpath-001's first phase 3 neoantigen win, LITESPARK-011 final in kidney cancer, and DASL-HiCaP in prostate. What a week ahead 🔬 #GUonc

VIKTORIA-1 #ESMO26 In PIK3CA-mutated HR+/HER2− advanced #BreastCancer post-CDK4/6i, gedatolisib-based regimens improved PFS vs alpelisib + fulvestrant, with fewer treatment discontinuations due to adverse events (4–5% vs 19%). @OncoAlert #bcsm @GustaveRoussy https://t.co/05cxWxH6M4

Updated results from VIKTORIA1 Study 2 confim PFS benefit. #ESMO26 Open questions from the Discussion @OncoAlert @BarbaraPistill2 https://t.co/V2kuf3V1iy

| VIKTORIA-1: Encouraging results in PIK3CA-mutated HR+/HER2− advanced breast cancer after CDK4/6i. Gedatolisib + fulvestrant ± palbociclib improved PFS vs alpelisib + fulvestrant, including in liver metastases. ▪️ORR: 43–59% vs 33% ▪️Median DoR: 19.4–27.8 vs 7.5 months ▪️Discontinuation of gedatolisib/alpelisib due to AEs: 4–5% vs 19% #ESMO26 @Larvol @myESMO @OncoAlert

#ESMO26 | VIKTORIA-1 – Study 2 In PIK3CA-mutant HR+/HER2− advanced breast cancer after CDK4/6i, gedatolisib + palbociclib + fulvestrant showed a PFS benefit over alpelisib + fulvestrant in patients with visceral metastases (9.8 vs 5.6 months; HR 0.52) and liver metastases (9.1 vs 4.6 months; HR 0.47). Superiority over an active control and lower rates of hyperglycemia are important strengths. However, my main question remains the added contribution of palbociclib. Gedatolisib + fulvestrant also showed substantial activity; although the small doublet arm does not establish equivalence, it raises questions about the additional toxicity and cost of the triplet. Weekly IV administration and stomatitis remain practical limitations. Excluding patients previously treated with PI3K/AKT/mTOR inhibitors also limits applicability to contemporary treatment sequencing.

VIKTORIA-1 shows benefit of Gedatolisib + fulvestrant +/- palbociclib significantly improved median PFS across subgroups as compared to alpelisb+fulv (in second line after CDK4/6i) #ESMO26 @OncoAlert @BarbaraPistill2 https://t.co/ItKZeazGji

#ESMO26 🇪🇸 | POP-DURVA Phase II 2 cycles of #durvalumab for preop stage I #TNBC (T1N0, n=78) 🔹sTILs increased from 10% to 22%. 🔹pCR 1.4% | MPR 11% #bcsm @OncoAlert @myESMO #BreastCancer https://t.co/RMrlme8XaJ

POP-Durva | #ESMO26 Short-course durvalumab reshaped the immune microenvironment in early TNBC, increasing median sTILs from 10% to 22%, despite limited pCR. Does immune activation translate into clinical benefit? @OncoAlert #BreastCancer #bcsm https://t.co/NOZqmPtHCK

🔹In POP-Durva, analyses on paired biopsies show immmune activation after 2 administrations of durvalumab in stage 1 TNBC 🔹Greater stromal TIL increases were associated with lower residual viable tumour #ESMO26 #ESMOAmbassadors @myESMO @Ribeiro2M @GustaveRoussy @LauBuisseret https://t.co/lozdaQD6JO

📌 Short-term preoperative durvalumab for stage I TNBC: First results from the phase II UNLOCK 14 - POP-DURVA trial ✨ Joana Ribeiro #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF https://t.co/eX5SsgpLDD

POP-DURVA 2 cycles of durvalumab for preop TNBC (T1N0) n=78 pCR: 1.4% @OncoAlert #ESMO26 https://t.co/k2ygp7vrVV

#ESMO26 | POP-DURVA In stage I TNBC, the clinical and immunological effects of a single dose of durvalumab without chemo were evaluated (n=71). - pCR: 1.7% - Objective response: 11.6% - Tumor shrinkage: 41.3% - Conversion to an inflamed phenotype: 33% of initially immune-negative tumors. A single dose of immunotherapy induced substantial immune activation, but pathological response was very limited. The main value of this study lies in identifying potential biomarkers of immunotherapy sensitivity rather than demonstrating the efficacy of a chemo-free approach. However, results after only 15 days of treatment cannot establish the efficacy of longer-term monotherapy.

#ESMO2026 #ESMO26 @myESMO השנתי של ESMO במדריד מציג גם השנה תמונה מורכבת של התקדמות באונקולוגיה, לצד תוצאות שעשויות לשנות את הטיפול בחלק מהגידולים, מתפרסמים גם מחקרים שליליים המזכירים לנו שלא כל שילוב טיפולי חדש אכן משפר את התוצאות הקליניות. 🏆 אונקולוגיה 🦀 הזוכים 🎉 עד כה... 1. DeLLphi-305 | סרטן ריאה מסוג תאים קטנים, מחלה נרחבת (ES-SCLC) אחת התוצאות הבולטות היא ממחקר פאזה III שבחן הוספת tarlatamab, נוגדן דו־ספציפי המכוון ל־DLL3, ל־durvalumab כטיפול אחזקה לאחר טיפול ראשוני במחלה שלא התקדמה. ההבדלים היו משמעותיים: חציון ההישרדות הכוללת (mOS): 21.1 לעומת 12.7 חודשים (HR 0.42). חציון ההישרדות ללא התקדמות (mPFS): 7.4 לעומת 1.9 חודשים (HR 0.34). המשמעות: תוצאה מרשימה, שעשויה לבסס אפשרות טיפולית חדשה באחזקה בקו הראשון בסרטן ריאה מסוג תאים קטנים. לצד עוצמת התועלת, יהיה חשוב להעריך גם את פרופיל הרעילות, ובפרט CRS ורעילות נוירולוגית, ואת היכולת ליישם את הטיפול בשגרה. 2. VOLGA | סרטן שלפוחית השתן החודר לשריר (MIBC) במחקר פאזה III נבחן טיפול פרי־אופרטיבי ב־enfortumab vedotin (EV) וב־durvalumab בחולים שאינם מתאימים לציספלטין או מסרבים לקבלו. דווח על שיפור בהישרדות ללא אירוע (EFS; HR 0.55) ובהישרדות הכוללת (OS; HR 0.58), לצד שיעור גבוה יותר של תגובה פתולוגית מלאה (pCR): 45% לעומת 10%. המשמעות: מדובר בתוצאה חשובה באוכלוסייה עם אפשרויות טיפול מוגבלות. היא מחזקת את מקומם של שילובים המבוססים על ADC ואימונותרפיה במחלה הניתנת לטיפול בכוונה מרפאת. עם זאת, חשוב להבחין בין זרועות הטיפול השונות במחקר, ובפרט בין משטר המבוסס על durvalumab לבין הוספת tremelimumab, שבה לא הודגם עדיין יתרון מובהק בהישרדות הכוללת. 3. STARBOARD | מלנומה מתקדמת עם מוטציית BRAF V600 המחקר בדק שילוב של encorafenib ו־binimetinib עם pembrolizumab לעומת pembrolizumab בלבד בקו הראשון. התוצאות הצביעו על שיפור משמעותי: שיעור התגובה האובייקטיבית (ORR): 70% לעומת 32.7%. חציון PFS: 33 לעומת 3.4 חודשים (HR 0.33). התועלת ב־PFS ובשיעור התגובה בולטת, אך הרעילות הייתה גבוהה יותר: תופעות לוואי בדרגות 3–4 דווחו ב־70% לעומת 39%. נתוני ההישרדות הכוללת עדיין אינם בשלים. המשמעות: שילוב מבטיח במיוחד, אך עדיין נותרו שאלות לגבי מיקומו ביחס לאפשרויות אימונותרפיה משולבת אחרות ולגבי מאזן התועלת והרעילות. 4. HERIZON-GEA-01 ו־G-HOPE-001 | טיפולים חדשים בסרטן הקיבה וה־GEJ שני מחקרים בולטים בתחום שבו הצורך בטיפולים יעילים עדיין גדול: HERIZON-GEA-01: zanidatamab בשילוב כימותרפיה, עם או בלי tislelizumab, בחולים עם מחלה מתקדמת HER2 חיובית. בזרוע הטיפול המשולש חציון OS הגיע ל־27 חודשים (HR 0.65), וכ־40% מהמטופלים היו בחיים לאחר שלוש שנים. G-HOPE-001: ה־ADC arcotatug tavatecan, המכוון ל־CLDN18.2, הראה שיפור בהישרדות הכוללת לעומת טיפול לבחירת הרופא: 10.2 לעומת 6.9 חודשים (HR 0.57). גם ההישרדות ללא התקדמות השתפרה. המשמעות: שתי התוצאות מחזקות את הפוטנציאל של טיפולים ממוקדים ושל ADCs בסרטן הקיבה וה־GEJ. חשוב לזכור שמדובר באוכלוסיות שונות ובקו טיפול שונה, ולכן אין להסיק מהן על יתרון ישיר של תרופה אחת על פני האחרת. ❌ המאכזב 😞 5. KEYNOTE-866 | סרטן שלפוחית השתן החודר לשריר במחקר נבחנה הוספת pembrolizumab לכימותרפיה מבוססת cisplatin ו־gemcitabine סביב הניתוח, בחולים המתאימים לציספלטין. המחקר לא השיג שיפור מובהק ב־EFS (HR 0.88; p=0.1366), ולא הודגם יתרון בהישרדות הכוללת. המשמעות: תוצאה שלילית עבור המשטר שנבדק. היא מדגישה שלא ניתן להסיק על הצלחת טיפול פרי־אופרטיבי אחד מהצלחת שילוב אחר, גם כאשר שניהם מבוססים על אימונותרפיה. 🔍 החשוד 🤨 6. INTerpath-001 | חיסון mRNA אישי במלנומה זהו מחקר חיובי מבחינת הישרדות ללא הישנות (RFS) והישרדות ☢️ רדיותרפיה: המחקרים העיקרים 🎯 7. DASL-HiCaP | סרטן ערמונית מקומי בסיכון גבוה מאוד במחקר פאזה III נבחנה תוספת darolutamide לטיפול הכולל דיכוי אנדרוגני (ADT) והקרנות, בחולים עם סרטן ערמונית מקומי בסיכון גבוה מאוד. דווח על הפחתה של כ־58% בסיכון לגרורות או למוות. שיעור ההישרדות ללא גרורות (MFS) לאחר ארבע שנים היה 95% לעומת 88%. המשמעות: תוצאה משמעותית התומכת בהעצמת הטיפול הסיסטמי בחולים המתאימים, על גבי טיפול הכולל הקרנות ו־ADT. חשוב להדגיש שהמחקר בוחן את תוספת darolutamide, ולא את יעילות ההקרנות לבדן. 8. MASTERPLAN | סרטן לבלב מקומי בסיכון גבוה מחקר פאזה II אקראי בחן הוספת SBRT במינון 40 Gy בחמש פרקציות לכימותרפיה בחולים עם סרטן לבלב מקומי בסיכון גבוה, לרבות מחלה גבולית לנתיחות ומחלה מקומית מתקדמת. התוצאות היו מעודדות: חציון OS: 22 לעומת 14 חודשים (HR 0.45). שיפור גם בהישרדות ללא התקדמות ובשליטה המקומית. לא זוהתה עלייה ברורה ברעילות החמורה שיוחסה ל־SBRT. המשמעות: זהו אות חיובי חשוב לתפקידה האפשרי של רדיותרפיה סטריאוטקטית בסרטן לבלב מקומי. עם זאת, המחקר כלל 74 מטופלים בלבד, ונדרש מחקר פאזה III כדי לאשר את התועלת, ובפרט את השפעתה על ההישרדות הכוללת. 9. SARON | סרטן ריאה אוליגומטסטטי המחקר בחן הוספת רדיותרפיה קונסולידטיבית לטיפול הסיסטמי בחולים עם NSCLC אוליגומטסטטי סינכרוני ללא שינויים גנומיים בני־מטרה (AGA-negative). נמצא שיפור בהישרדות ללא התקדמות: חציון PFS של 13.9 לעומת 8.9 חודשים (HR 0.64). גם השליטה המקומית השתפרה, עם שיעור כישלון מקומי לאחר 12 חודשים של 13% לעומת 39.5%. אולם, לא הודגם יתרון בהישרדות הכוללת: חציון OS של 31 לעומת 28 חודשים (HR 0.99). המשמעות: המחקר מדגים היטב את ההבדל בין שיפור בשליטה המקומית ובהישרדות ללא התקדמות לבין הארכת חיים. התוצאות אינן מבטלות את ערכה של הרדיותרפיה בחולים נבחרים, אך אינן תומכות בקביעה שתוספת טיפול מקומי משפרת OS באוכלוסייה שנבדקה. לסיכום: לצד ההתלהבות מתוצאות חיוביות, צריך להקפיד להבחין בין מחקר פאזה III למחקר פאזה II, בין ניתוחי ביניים לתוצאות בשלות, ובין שיפור במדדי המחלה לבין הוכחה להארכת חיים. *הסקירה משקפת את הנתונים שדווחו עד 24 באוקטובר 2026; חלק מהמחקרים עדיין דורשים מעקב נוסף ואימות של התועלת ארוכת הטווח.

Phase II SARON (n=140,NSCLC): ​Consolidation RT + 1L SACT improved: • PFS: 13.9 vs 8.9 mo (p=0.03) • 12-mo local failure: 13% vs 39.5% (p<0.01) ​No OS benefit (31 vs 28 mo; p=0.95). Grade ≥3 toxicity: 28.6% both arms. ​#ESMO26 @Larvol @OncodailyLung https://t.co/99mkC2CR2j

🚨 #ESMO26 Lung Cancer: the 10 studies that best capture where the field is moving @OncoAlert What stands out to me from the @OncoAlert faculty selection is how much the lung cancer landscape is shifting toward smarter sequencing, biomarker-defined combinations, and more selective treatment intensification. 🫁 Top Ten from Madrid: 1️⃣ DeLLphi-305 — tarlatamab + durvalumab in 1L ES-SCLC maintenance 2️⃣ Krascendo 1 — divarasib vs sotorasib/adagrasib in KRAS G12C NSCLC 3️⃣ SAFFRON — osimertinib + savolitinib after osimertinib in EGFRm/MET+ disease 4️⃣ OptiTROP-Lung04 — sac-TMT after EGFR-TKI 5️⃣ OptiTROP-Lung06 — sac-TMT + pembrolizumab in PD-L1-negative NSCLC 6️⃣ PERSEE — pembrolizumab ± chemotherapy in PD-L1 ≥50% 7️⃣ SANOVO — savolitinib + osimertinib in 1L EGFRm/MET-overexpressed NSCLC 8️⃣ IFCT-2103 DIAL — continue pembrolizumab vs observation at 6 months 9️⃣ PANKU-Lung01 — iza-bren after third-generation EGFR TKI 🔟 SARON — consolidation RT in oligometastatic NSCLC 🎯 Why this matters: these studies are not just adding new drugs. They are refining when to intensify, when to combine, when to continue, and when biology should drive the next step. That is the real value of a “Top Ten” list: not more information — better prioritization of the data most likely to influence practice. @christine_lovly @GlopesMd @DrSanjayPopat @StephenVLiu @jillfeldman4 @UOzkerim @DrMirallas @CharuAggarwalMD @peters_solange @JordiRemon #lcsm #OncoAlert #ESMO26 #LungCancer #NSCLC #SCLC #PrecisionOncology

Congrats to the SARON investigators! Important randomized data for a question we face all the time. 👏 Consolidation RT improved local control and PFS, but no OS benefit demonstrated: HR 0.99 (95% CI 0.63-1.55). The RT details caught my eye. Of 62 pts who received RT, 51 had conventional treatment to the primary and only 11 had primary SABR. About 53% of the full cohort had N2/3 disease. Side note: in the separate 13-pt ESTRO safety substudy, the most common schedules were 55 Gy/20 fx to the primary (10/13 pts) and 27 Gy/3 fx to thoracic mets (4/14 lesions). Those are substudy doses, not the dose distribution for the whole trial. Curious how pts who actually received SABR to all sites did. That would be exploratory, but I'd like to see the dose/volume details and patterns of failure before generalizing these results to patients receiving total consolidation. Looking forward to the full paper! #ESMO26 #radonc https://t.co/3AtnSapEMk

After CDK4/6i in HR+ MBC, the control arm is the story at #ESMO2026. FINER: fulvestrant alone, median PFS 1.9 mo. Ipatasertib + fulvestrant 5.4 mo, HR 0.68. In AKT pathway-altered tumors, HR 0.55.
FOURLIGHT-1: atirmociclib, a CDK4-selective inhibitor, 9.4 vs 6.6 mo with investigator's choice, HR 0.60. 85 to 92% randomized within 3 months of their last CDK4/6i. Fulvestrant alone after a CDK4/6i is close to no treatment. FINER helped even without selection, but with toxicity FOURLIGHT-1 tests whether keeping CDK4 pressure on, more selectively, beats switching. #bcsm #ESMO26 @myESMO

📌 Proffered paper 2: Breast cancer, early and advanced stage 👉🏻Overall survival results of the CCTG/BCT MA.40/FINER study A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for HER-2 negative and ER+ metastatic BC ✨ Andrew Redfern #ESMO26 🇪🇸 @OncoAlert #OncoAlertAF

FINER demonstrates ipatasertib + fulvestrant improves PFS (but not OS) for both ITT and AKT pathway altered cohorts with notable AEs #ESMO26 @OncoAlert https://t.co/3SzRMFV2ew

#FINER fulvestrant +/- ipatasertib (AKTi) 45% of pts were pathway altered PFS lengthened in ITT HR 0.68 and AKT altered cohorts HR 0.55 93% diarrhea, pretty high G2/3 rates #ESMO26 #ESMOAmbassadors https://t.co/QNFFn9uJog

At #ESMO26 Proffered Paper 2️⃣ on #breastcancer Results of the FINER trial Ipatasertib + fulvestrant does not improve OS, neither overall nor in the AKT-mut cohort Improvement in PFS and longer time to subsequent systemic tx or death @OncoAlert https://t.co/56eGEuV7sN

#ESMO26 | FINER In HR+/HER2− mBC, ipatasertib + fulvestrant failed to demonstrate an OS benefit despite improving PFS (26.7 vs 25.8 mo; HR 1.14). No OS benefit was observed in patients with AKT pathway alterations either (HR 1.14)!!! I’m eagerly awaiting the presentation details to better understand why the PFS benefit did not translate into an OS advantage.

PACE-LUNG #ESMO26 ctDNA-guided treatment intensification in EGFR-mutant NSCLC: Early molecular response as a guide to adaptive therapy 🫁 #LungCancer @OncoAlert #LCSM https://t.co/VPeBO6ig5C

ctDNA with 1L EGFRmut regimens ❓what does it tell us ❓what does it add We already know: 🔸EGFR ctDNA +ve @ baseline = poorer prognosis 🔸 Clearing EGFR ctDNA with treatment = better prognosis 🔸 EGFR ctDNA -ve @ baseline = no additional benefit of chemo/osi or ami/laz over osi alone PACE-Lung: 🔹ctDNA +ve at baseline 🔹If also ctDNA after 4wks on Osi, add chemo (x4 cycles) 🔹 mPFS = 17.8m [similar to FL2] FLAURA-2: 🔹 Focus on ctDNA +ve at baseline popn 🔹Osi+chemo improves OS & PFS irrespective of ctDNA clearance 🔹ctDNA +ve at baseline is prognostic, not predictive What do we know now? 🤔 If EGFR ctDNA -ve at baseline (20% popn), prognosis is better, and adding chemotherapy to osimertinib, or using ami/laz instead of osimertinib add little (no) benefit 🤔 If EGFR ctDNA +ve at baseline (80% popn), prognosis is worse. However, clearance or not of ctDNA does not help us refine treatments 🤔 If EGFR ctDNA +ve at baseline, osi+chemo or ami/laz is better than Osimertinib alone Brilliant discussion by @LeXiuning 👏 #ESMO26 #LCSM

Thoughtful trial: PACE-LUNG demonstrates that ctDNA-guided treatment intensification is feasible and results in a 17.8 m PFS that compares favorably with historical studies. @myESMO #ESMO2026 @OncoAlert https://t.co/XEcwq2DtIs

PACE lung: treatment escalation in ctDNA non clearers. Would be nice to know more about the ctDNA positive group co-mutations. #LCSM #ESMO26 https://t.co/s4U6B9csMH

#ESMO26 Dr. Martin Sebastian presents PACE-LUNG: phase II study of osimertinib monotherapy for EGFR NSCLC with ctDNA at 3w and if positive, add 4 cycles of chemotherapy. 72/255 were ctDNA positive at 3w. mPFS 17.8m and OS 31.5m from start of osi - no comparator but encouraging. https://t.co/6VbL02UEJ5

#PACELung trial CTDNA guided tx intensification is feasible; results comparable to historical data #ESMO26 https://t.co/saZAHczih1

🆙#ESMO26 Rapid Oral I: #LCSM Mets 🔥PACE-LUNG (AIO-TRK-0422/ass): A Multicenter, Single-Arm, Phase II Clinical Trial Evaluating the Efficacy of Additional Chemotherapy for Patients With EGFRm NSCLC With the Continued Presence of Plasma ctDNA EGFRm at Week 3 After Start of Osimertinib First-Line Treatment 🎙️Dr. Martin Sebastian 🔢LBA73 🎯ctDNA-Guided Treatment Intensification Feasible 🎯mPFS 16.3mo From Start of Chemo ( 29% of Screened Pts Had Persistent ctDNA) 🎯mOS 29.2mo, 24-Mo OS 65.4% ☑️NCT05281406 🔗 https://t.co/E2MIRGnkpb @OncoAlert @Larvol @myESMO @IASLC @EGFRResisters

#ESMO26 Eclypse trial https://t.co/SQXS2rnAPq

ECLYPse phase II: continuing encorafenib + cetuximab with FOLFIRI beyond progression in BRAF V600E mCRC. 👉 mPFS 7.1 months 👉 mOS not reached 👉 ORR 15% Intriguing signal! what drives the benefit though? #ESMO26 #ESMOAmbassadors https://t.co/hlMQw55G6Y

Pilot trial of ECLYPse Phase II of continuing encorafenib + cetuximab + FOLFIRI in 2nd line #BRAF MT #colorectal #cancer with benefit of continuation beyond PD. Primary endpoint = 6M PFS was met; too early for OS. @OncoAlert @oncodaily #ESMO26 #cancerresearch https://t.co/w5nI4Qowoh

Encorafenib plus cetuximab beyond progression in combination with FOLFIRI in BRAF V600E mCRC progressing on EC: Results from the ECLYPse phase II trial #ESMO26 #ESMOAmbassadors 👉 mPFS: 7.1 👉 mOS: NR 👉ORR 15% 🧐Interesting signal to continue EC, more translational data would be great @myESMO @ASCO

#ESMO26 Bricket trial https://t.co/zbWo8X1e2x

BRICKET trial: no signs of activity for targeted therapy rechallenge in BRAF-mt mCRC. Post-BREAKWATER era opens new questions for innovative trials in this challenging setting 🧬 Proud to have contributed to the BRICKET experience, learning so much along the way! #ESMO26 @myESMO https://t.co/rJJm5cnNEO

TRIDENTE “positive”, BRICKET “negative” ?? Prior responder selection & added binimetinib may explain differing ORR outcomes. Yet mPFS was almost identical: 2.8 vs 2.9 months. 🧐 Reminder to look beyond trial labels: how durable is the benefit? #ESMO26 #ESMOAmbassadors @OncoAlert https://t.co/V6R2gxa0I9

Phase II GONO BRICKET trial evaluating #BRAF MT #colorectal #cancer to allow re-treatment (N=16) in pts with prior benefit and >/=4M between therapies. The trial was UNABLE to meet primary endpoint resulting in a 0% RR. Therefore retreatment does not appear to provide additional benefit. @OncoAlert @oncodaily #cancerresearch #ESMO26

BRICKET by GONO-GI: ctDNA-guided re-treatment with enco/cet in chemorefractory BRAF-V600E mut mCRC - 11/30 pts with resistance ctDNA mutations - no activity signals #ESMO26 @OncoAlert @ChiaraCrem1 https://t.co/ZKU5BTFZhO

#ESMO26 Day 1 highlight for me: MASTERPLAN, now in Lancet Oncology. Radiation and pancreatic cancer have a complicated history. ESPAC-1 suggested adjuvant chemoradiation hurt. LAP07 and CONKO-007 couldn't show an OS benefit after chemo. A021501 closed its RT arm for futility. PREOPANC-2 was a draw. We walked through the adjuvant side of this story in Sem Rad Onc last year: https://t.co/qGkMfyjghA So why is MASTERPLAN different? Phase 2, 14 sites in Australia and NZ (can i just say I love the Aus-NZ studies). 74 patients with high-risk localized PDAC, randomized 2:1 to chemo ± SBRT 40 Gy/5 after induction. 12-mo locoregional recurrence 20.2% vs 52.0%, sHR 0.44, p=0.022 
PFS 11.9 vs 6.3 mo, HR 0.44 
OS 22.0 vs 14.0 mo, HR 0.45 
Grade ≥3 AEs 70% vs 64%. Why did this one work when others didn't? The rad oncs can explain the physics better than I can. I just read it as better tumor zap zap. Does it change practice? Maybe. I think we need to have a deeper conversation at every tumor board, but the juice seems worth the squeeze. @OncoAlert @TheGutOncLab @Onco_Nexus https://t.co/rt0c35UkcW