ESMO 2026 Trial Results & Physician Discussion

would benefit from virotherapy as a first-line treatment. Fortunately, immunotherapy as a first-line treatment is emerging as the most promising therapeutic option, as we saw this past weekend at ESMO with the case of Tarlatamab-Durvalumab, among others. 11/14

The trial: DeLLphi-305, 563 patients, NEJM and ESMO this week. After standard chemo plus immunotherapy: durvalumab alone vs durvalumab + tarlatamab as first-line maintenance. Median survival: 21.1 vs 12.7 months. Death risk: 58% lower (relative, HR 0.42).

THE COMBINATION OF TARLATAMAB ( AMGEN ) + DURVALUMAB ( ASTRAZENECA) REDUCED THE RISK OF DEATH BY 58% AS FIRST-LINE MAINTENANCE TREATMENT IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ES-SCLC) https://t.co/wQpCZiGzmr #pharmamar @expansioncom @Nasdaq #lurbinectedin @FT @FDA @EMA_News https://t.co/Hc0kO5dPIv https://t.co/9MvUKf6kv4

DAY 2 — DeLLphi-305 Tarlatamab + durvalumab maintenance in extensive-stage SCLC improved median OS: 21.1 vs 12.7 months (HR 0.42). A substantial survival gain. Cytokine release syndrome affected nearly half of patients, highlighting the need for monitoring. https://t.co/MDLz4Ov8rv

SCLC: tarlatamab is moving earlier. DeLLphi-305: 1L maintenance + durva vs durva: est. mOS 21.1 vs 12.7mo (HR 0.42; p<0.001) DeLLphi-304 (23mo follow-up): 2L vs chemo: mOS 13.6 vs 8.4mo (HR 0.62) How should we sequence it? @sands_jacob @StephenVLiu @OncoAlert @OncoDaily #ESMO26

🎗️ من مدريد – المؤتمر الأوروبي للأورام #ESMO2026 من أهم أبحاث المؤتمر في الجلسة الرئاسية: دراسة DeLLphi-305 في سرطان الرئة صغير الخلايا. هذا النوع من سرطان الرئة سريع الانتشار. 🔬 إضافة العلاج المناعي الحديث تارلاتاماب إلى دورفالوماب كعلاج وقائي بعد العلاج الأولي أدت إلى:
✅ انخفاض خطر الوفاة بنسبة 58%
✅ البقاء على قيد الحياة بعد سنة: 79.4% مقابل 53.3%

📄 Amgen/AstraZeneca プレスリリース: Tarlatamab + Durvalumab in Extensive-Stage SCLC. ESMO 2026発表. https://t.co/OWWwFLZmGF

There's encouraging news for people facing extensive-stage small cell lung cancer. In the phase 3 DeLLphi-305 trial, a first-line maintenance combination of tarlatamab and durvalumab extended median overall survival by more than eight months compared… https://t.co/gQoldEvVrK https://t.co/BdlM55liyN

Changes soon (NICE/CDF pending) 1. DeLLphi-305 Tarlatamab + durvalumab as first-line maintenance in SCLC. New SoC. median OS 21.1m vs 12.7m. NEJM 2. SAFFRON Osimertinib + savolitinib new SoC after osimertinib progression with MET driven resistance. OS 17.8m Vs 12.9. NEJM #ESMO26 https://t.co/noByEiHPva

In extensive-stage small-cell lung cancer, many of our patients never make it to second-line therapy. Adding tarlatamab to durvalumab in first-line maintenance gives them our most active agent while they can still benefit. 80% were alive one year after starting maintenance, including patients with brain and liver metastases. CRS was mostly limited to the first two doses, with no serious neurologic events. Small steps in SCLC, but this one matters for our patients. 💙 #ESMO26

🫁 #ESMO26 DeLLphi-305 (ph III): tarlatamab + durvalumab as maintenance after 1L chemo-IO in ES-SCLC. OS 21.1 vs 12.7 mo (HR 0.42) PFS 7.4 vs 1.9 mo (HR 0.34) Potential new maintenance standard. Watch for CRS/ICANS. #lcsm https://t.co/rFSWZC2Ty7

🔥Lung🫁 #ESMO26 #LCSM 🎉Again🔂 4⃣ @NEJM 🎯DeLLphi-305 🎯OptiTROP-Lung06 🎯Krascendo 1 🎯SAFFRON 2⃣ @TheLancet 🎯PANKU-Lung01 🎯HERON-Lung01 3⃣ @Annals_Oncology 🎯PERSEE 🎯DeLLphi-304 🎯NEOTORCH 1⃣ @Nature 🎯NeoCOAST-2 1⃣ @NatureMedicine 🎯MDT-BRIDGE 1⃣ @JCO_ASCO 🎯Dalmelitinib Plus Aumolertinib @OncoAlert @Larvol @myESMO @IASLC @ASCO @EGFRResisters @KRASKickers @metcrusaders

📈 Update on tarlatamab in 2L ES-SCLC from DeLLphi-305. 🧀 Small fraction of patients obtained long-term benefit as shown by 16% of patients w/o disease progression at 16 months. ✅ Better OS and tolerance compared to chemo, though. #ESMO26 #LCSM https://t.co/0QLRIApP8x

Been chewing on non-GI data. This readout is in lung but highly relevant to high grade extrapulmonary NET. DeLLphi-305 at #ESMO26. Tarlatamab, a DLL3 x CD3 T-cell engager, added to durvalumab as 1L maintenance in extensive-stage SCLC. Design
• Phase 3, randomized, open-label, n=563
• durva + platinum/etoposide induction -> Durva + tarlatamab vs durva alone
• OS primary, interim analysis OS 21.1 vs 12.7 mo, HR 0.42
12-mo OS 79% vs 53% ES-SCLC survival creeping from around a year, now nearly at 2 years. DLL3 isn't a lung target, it's a neuroendocrine one. (Right @UGrewalMD ? This is your thing for sure). Extrapulmonary NEC has the same story SCLC had: a short response to chemo, then minimal on-label options. The catch is CRS and ICANS, so you need the infrastructure. Maintenance Tarla seem well worth the survival advantage. @OncoAlert @TheGutOncLab @Onco_Nexus

Tarlatamab-durvalumab maintenance by Perol and @sands_jacob @NEJM for ES-SCLC discussed by @StephenVLiu at @myESMO Take: DeLLphi-305, phase 3, n=563, maintenance after 1L chemoimmunotherapy without progression. Median OS 21.1 vs 12.7 months (HR 0.42, P<0.001). Median PFS 7.4 vs 1.9 months (HR 0.34). 12-month OS 79.4% vs 53.3%. Grade ≥3 events 46.8% vs 40.6%; CRS, mainly grade 1-2, in nearly half the tarlatamab arm. As expected D-305 moves tarla into first-line maintenance and nearly doubles median survival in a disease where 12-13 months has been the ceiling for years. If we are honest, unless we make big change due to CRS and tocilizumab it will be hard to make tarlatamab mainstream to most patients even in the US and LMICs. #LCSM #SCLC #clinicaltrials

Historical trial 🚨 DeLLphi-305 trial 1L maintenance ES-SCLC Tarlatamab + durvalumab vs durvalumab 👉 OS 21.1 vs 12.7 mo (HR 0.42) 👉 PFS 7.4 vs 1.9 mo (HR 0.34) 🛡️ CRS 49.6%, mostly G1–2; ICANS 1.1% 💡 Biggest 1L maintenance signal in ES-SCLC ➡️ likely new standard ⚠️ Interim analysis, open-label; probably need to use durval with induction now to avoid insurance issues. Adding to https://t.co/L7deCjtEzH shortly 👨‍💻 📄 https://t.co/TcoIbeN92v

DeLLphi-305 is a real OS win, HR 0.42, and since many SCLC pts never reach 2L, giving tarla early makes sense. But only 33 of 281 control pts got tarla later, so the trial can’t tell us how much of the gain is early tarla vs any tarla at all. https://t.co/900ba8dn9q

#DeLLPhi305 Low US enrollment in this pivotal #SCLC trial is NOT surprising. Regulatory hurdles, costs & complexity push sponsors to conduct trials faster ex-US—even for drugs destined to be used at greater rates by US patients. Why it matters: ▶️ Less evidence on implementation & AEs in diverse populations ▶️ Fewer opportunities for US investigators to shape drug development early We need faster, more inclusive trials! 🔬#clinicaltrials #ESMO26 @SclcSMASHERS @GlopesMd

I’m trying to understand the degree of immortal time bias influencing the absolute OS values and not sure which chemotherapy-alone dataset to reference. If we benchmarked it to the control arm of CASPIAN (cis-etop alone) it would cut the OS estimates for DeLLphi-305 in half since 55% progressed by 6 months. Thoughts? #ESMO26

Heartfelt congratulations to @sands_jacob for an outstanding presentation that conveyed both the scientific significance of these results and what they mean for our patients. Words cannot describe what we experienced yesterday with #ippokratis_korantzis @newsincancer at #ESMO2026 in Madrid . A packed auditorium, warm applause and profound emotion. A moment of immense pride for our team and our contribution to #DeLLphi305 .A #landmark study in extensive-stage small-cell lung cancer #ESCLC : adding #tarlatamab to #durvalumab as #maintenance therapy after initial chemoimmunotherapy reduced the risk of death by 58%, with mOS of 21.1 versus 12.7 months from randomisation.A major step forward in a disease where progress has been exceptionally difficult for so many years.And through it all, our thoughts were with our #patients .With their trust, their fears and their hope for more time with the people they love..with fewer symptoms and a better quality of life.We dedicate this special moment to them and their families, whose trust made this research possible.With deep gratitude and an even greater sense of responsibility for what comes next. #4th_Department_of_Medical_Oncology_and_Clinical_Trials_Unit #one_of_us_oncology  #oncodaily #thoraciconcology #clinicaltrials #LungCancerResearch #ClinicalResearch #PatientCenteredCare #BetterOutcomes #HopeThroughResearch #AdvancingScience #StrongerTogether #united #Interbalkan_Medical_Centre @AthensMedical #D_Oncology_Department #ClinicalResearch #THESSALONIKI #InternationalCollaboration #International_Oncology_Center @myESMO @oncodaily

Could DeLLphi-305 redefine first-line maintenance in ES-SCLC? At #ESMO26, Dr. Jacob Sands presented striking Phase III results: Tarlatamab + durvalumab vs durvalumab: OS: 21.1 vs 12.7 months (HR 0.42) PFS: 7.4 vs 1.9 months (HR 0.34) A potential practice-changing result for SCLC. #DeLLphi305 #Tarlatamab #LCSM @OncoDaily @OncoAlert @myESMO #ESMO26

@430Yang Impressive data from DeLLphi-305 - median OS 21.1 vs 12.7 months and ~79% vs 53% alive at 1 year with tarlatamab + durvalumab maintenance. Clear progress in a tough disease, but cost and access will likely limit who actually gets it for now.

Landmark data from DeLLphi-305 in 1L maintenance Tarlatamab #TCE + Durvalumab presented on Day 2 of Presidential #ESMO26 ✅ mOS 21.1m vs 12.7m with HR 0.42 ✅ ORR 26.4% vs 4.1% ✅ Almost 50% G1-2 CRS with only 1 patient with G3 ⭐️All treatment delivered as outpatient with post infusion monitoring 1-2 hours (6-8 hours in EU) Many congratulations to @sands_jacob and @StephenVLiu’s thoughtful and masterclass discussion. @AmgenOncology @Amgen 👏🏼👏🏼👏🏼 @myESMO

Practice changing results from DeLLphi-305 #ESMO26 and UK NICE needs to quickly help make this available. Attrition post-1L is high so bringing tarla forwards makes sense. Minimal G3 CRS/ICANS probably from early cytoreduction of tumour. OP delivery possible (2 hour monitoring). https://t.co/Srgzj7ph5Z

#ESMO26 Presidential I: Dellphi305: Ph III Maint Tarla+Durva v Durva in 1L ES SCLC🔥 - mOS HR 0.42 (21.1m v 12.2m, p<0.001) - superb discussion by @StephenVLiu highlighting change in biology of SCLC post Tarla, oligomet paradigms seen - rousing call for access @OncoAlert #LCSM https://t.co/apE2kEqmll

DeLLphi-305 appendix @NEJM : a DLL3 T-cell engager was given at progression to 64% of control patients in the USA vs 5% in Europe. OS HR: Americas 0.82 (0.39–1.71) vs Europe 0.36. Small subgroups, but in the TCE era OS depends on 2L access. Same trial, different answer. #ESMO26 https://t.co/GwhlVg8T1x

A masterclass in how to deliver an outstanding scientific discussion at #ESMO26! 👏 Highly recommend watching @StephenVLiu’s discussion of the incredible DeLLphi-305 results presented by @sands_jacob. What made it so effective? 🔹 Started with the unmet clinical need, not the trial data. 🔹 Critically appraised the evidence while explaining what it means for patients. 🔹 Moved beyond what the trial showed to why it matters and what questions come next. 🔹 Connected efficacy, safety and real-world access into one compelling narrative. 🔹Masterful delivery. Purposeful pauses, variation in tone and pitch, and virtually no filler words. He finished with a powerful reminder: “innovation loses impact if it doesn’t reach the patients who need it most.” A great discussant doesn’t just summarise or repeat results. They help us understand what changes, what remains uncertain and what the field must do next. Science communication at its best! 👏

🫁🫁 DeLLphi-305 🫁🫁 💥 This is a hypothesis and falls within the realm of speculation. 💥I am specifically treating the OS on the CASPIAN side as a hypothesis. 💥Although this is a simple calculation, the OS for first-line treatment of ES-SCLC is 34.0 months, and it is possible that OS figures close to this value may be observed in real-world clinical practice. 💥💥IMO #ESMO2026 #SCLC #Lungcancer

SMALL CELL LUNG CANCER MAY HAVE JUST ENTERED A NEW ERA! For decades extensive stage small cell lung cancer has challenged oncologists with rapid growth! Early dissemination! Initial chemotherapy sensitivity! And devastating relapse! Today at ESMO 2026 we witnessed something remarkable! The Phase 3 DeLLphi 305 trial enrolled 563 patients whose cancer had not progressed following platinum etoposide and durvalumab! Investigators compared maintenance durvalumab alone against durvalumab combined with tarlatamab! THE RESULTS DEMAND ATTENTION! Median overall survival improved from 12.7 months to 21.1 months! The hazard ratio for death was 0.42! Median progression free survival increased from 1.9 months to 7.4 months! At one year approximately 79% of patients receiving the combination remained alive compared with 53% receiving durvalumab alone! These are not simply changes in tumor measurements! These are meaningful survival gains in one of the most aggressive malignancies we treat! BUT WHY DOES THIS MATTER BIOLOGICALLY? Small cell lung cancer frequently expresses DLL3! Tarlatamab is a bispecific T cell engager that binds DLL3 on malignant cells and CD3 on T lymphocytes! It physically brings the immune system into contact with cancer! Durvalumab blocks PD L1 mediated immune suppression! Together these agents may help overcome complementary barriers to antitumor immunity! This raises an extraordinary possibility! Perhaps the future of small cell lung cancer is not simply stronger chemotherapy! Perhaps it is earlier and more effective immune redirection! BUT WE MUST ASK HARDER QUESTIONS! Why do some patients achieve durable disease control while others progress? Could circulating tumor DNA identify molecular relapse before radiographic progression? Could single cell sequencing reveal exhausted T cell populations that predict resistance? Could spatial transcriptomics identify tumors where T cells cannot effectively reach DLL3 expressing malignant cells? Could serial tumor and blood sampling reveal whether DLL3 expression changes under treatment pressure? And could adaptive trials use these biomarkers to identify who benefits from earlier treatment? We must also confront toxicity! Cytokine release syndrome occurred in approximately half of patients receiving the combination and was predominantly low grade! Neurotoxicity and the need for specialized monitoring cannot be ignored! Longer survival must be accompanied by preserved quality of life! THE NEXT EXPERIMENT MATTERS! I would propose a prospective translational study combining serial circulating tumor DNA! DLL3 expression! T cell receptor sequencing! And immune profiling before and during maintenance! The goal would be to identify the biology of durable responders and develop rational combinations for patients who develop resistance! As an oncologist caring for patients with advanced cancer I believe our responsibility extends beyond celebrating positive trials! We must determine how to convert longer survival into durable remission! And eventually cure! Congratulations to Jacob Sands and the international DeLLphi 305 investigators! The next chapter should be written through collaborative science! Could DLL3 directed immune engagement combined with molecular monitoring become the foundation for preventing small cell lung cancer relapse? Reference! ESMO 2026 LBA3! DeLLphi 305! New England Journal of Medicine! DOI 10.1056/NEJMoa2609482 https://t.co/0RRJDimblK #ESMO26 #SCLC #LungCancer #Immunotherapy #CancerResearch

"Equitable access to cross-over: at time of POD, only 12.2% of ITT population in the durvalumab arm (34/278) and 18.9% (34/179) of those who received subsequent anti-cancer therapies had access to tarlatamab." @drshieldsmd https://t.co/PuYlaxfI4q https://t.co/RDMQKqGIMK

DeLLphi-305 - #Tarlatamab + #Durvalumab as 1L Maintenance in ES-SCLC https://t.co/lZFpznzlGb Phase 3 #DeLLphi305 (Sands J et al.; ESMO 2026 LBA3, #NEJM): adding tarlatamab (DLL3 x CD3 T-cell engager) to durvalumab improved OS vs. durvalumab alone after induction chemo-IO.

Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer | New England Journal of Medicine https://t.co/967O8gzTKV

Today, the Phase 3 results of DeLLphi-305 (@AmgenOncology @AstraZeneca) were presented by @sands_jacob at #ESMO26. DeLLphi-305 delivered an unprecedented OS improvement (21.1 vs 12.7 mo, HR 0.42) for patients receiving tarlatamab + durvalumab, compared to durvalumab alone, in 1L maintenance after chemoIO induction for ES-SCLC. Studies like these provide renewed hope. However, this data brings forth multiple concerns regarding international access to care, interpretation of contribution of parts, patient selection, and sequencing. 1️⃣ Equitable access to cross-over: at time of POD, only 12.2% of ITT population in the durvalumab arm (34/278) and 18.9% (34/179) of those who received subsequent anti-cancer therapies had access to tarlatamab. This speaks to the global need to expand access to this life-saving therapy, as DeLLphi-301 demonstrated this impact with accessibility promptly available here in the USA as early as May 2024. Yet, @SclcSMASHERS all over the world still do not have this option even at relapse. 2️⃣ Line of therapy: while attrition to 2L may be significant in some practices & highlights the need to maximize proactive support & early palliative care, is there clear evidence of synergy with ICI+DLL3 TCE to transform outcomes, or is the effect additive? Preclinical data suggested synergy with this combination approach. However, within subgroup analyses of those receiving tarlatamab in subsequent treatment, particularly in the USA, it appears there is signal of additivity, given the nullification of OS benefit with DLL3 TCE cross-over (in those receiving it as 2nd LOT). Outside of risk of attrition, what variables favor using tarlatamab in 1LM vs 2L? Is the NE biology still preserved? Is the function of the immune system equivalently preserved following <4 weeks post chemoIO with myelosuppression? 3️⃣ Patient selection: Stratification with effective predictive biomarkers are key to know who can avoid any intensification, as they may be a durable ICI responder to monotherapy ICI. Who can we avoid tarlatamab every 2 weeks indefinitely? Who should receive lurbi + atezo? Or durva + tarla? More translational SCLC based biomarkers, beyond DLL3, are clearly of high unmet need to guide strategies. 4️⃣ Sequencing: if we use tarlatamab+durvalumab in the 1LM, what’s next? At POD, what approved option remains? Lurbi remains approved in the 1LM, but not at relapse. I-DXd BLA was voluntarily withdrawn. Trials are key, but enrollment for most global studies is brisk, particularly in the USA where enrollment is ~20% or less of the total cohort. @SclcSMASHERS @LUNGevity @IASLC @ASCO @NCCN @LungCancerEu @lcrf_org @OncBrothers @OncoAlert @oncodaily @OncLive @lungoncdoc @RManochakian @LauraAlderMD @LaurenByersMD @Annechiangmd

Amgen's tarlatamab + durvalumab extended median survival to 21.1 months vs 12.7 in extensive-stage small cell lung cancer at ESMO, cutting death risk 58% in Phase 3. A new maintenance standard for one of oncology's toughest cancers.

Big update in extensive-stage SCLC. DeLLphi-305 showed that adding tarlatamab to durvalumab maintenance improved median OS from 12.7 to 21.1 months and PFS from 1.9 to 7.4 months, measured from maintenance randomization. These are impressive results, and I can see this changing our maintenance discussions with patients. I’m still thinking through two questions. First, where does this leave lurbinectedin + atezolizumab maintenance from IMforte? The DeLLphi-305 numbers look better, but we cannot establish superiority by comparing results across trials. Second, what do we give after progression on tarlatamab + durvalumab? Trials, platinum rechallenge in selected patients, and lurbinectedin/topotecan are considerations, but we need better evidence in patients whose disease has progressed on tarlatamab. Keeping tarlatamab for second line is an understandable argument. In clinic, though, we also see patients deteriorate too quickly to receive the next treatment. One detail I’d particularly want to examine is how many patients in the control arm received tarlatamab after progression. That matters when discussing early treatment versus reserving it for relapse. I’m encouraged by these results. Alongside working out the best sequence, we’ll need to make treatment accessible and have the staffing, monitoring and caregiver support to deliver it safely. https://t.co/IKFyOZ8ln6 #ESMO26 #LCSM #SCLC @UVMcancercenter @myESMO @lcfamerica @SclcSMASHERS

Not my disease, but DeLLphi-305 is probably the result of ESMO 2026. #Tarlatamab, a DLL3 x CD3 T-cell engager, added to durvalumab as first-line maintenance in extensive-stage small cell lung cancer. Median OS 21.1 vs 12.7 mo, HR 0.42. 12-month OS 79% vs 53%. Why this matters: for 30 years, median survival in ES-SCLC sat around 10 to 13 months. Adding IO to chemo moved it about 2 months. This moves it about 8, with an HR rarely seen in any metastatic disease. Three points beyond lung:
A T-cell engager works in a solid tumor.
Maintenance is where you add the new drug: after induction, on lower disease burden.
DLL3 is a neuroendocrine target. Cost: CRS and ICANS need monitoring infrastructure. #lcsm #ESMO26 @myESMO

In phase 3 of the DELLphi-305 Trial involving patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC), the median OS was 21.1 months when tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 (DLL3) and CD 3 was added to durvalumab, an anti-programed death ligand 1 agent, when administered as combination maintenance therapy vs 12.7 months with durvalumab alone with better progression-free survival. This significant improvement was achieved with the use of a combination of both immunotherapeutic agents after initial chemo-immunotherapy and after first remission when it is unclear. Adverse events (AEs) of grade 3 or higher occurred in 46.8% of patients receiving combination therapy and 40.6% in those who received durvalumab alone. Cytokine release syndrome (CRS) of grade 1 or 2 was seen in nearly half the patients receiving the combination therapy. ES-SCLC is a highly aggressive and rapidly progressing type of adenocarcinoma with poor prognosis. It occurs when cancer has spread beyond the lung where it started and metastasized to the contralateral lung, distant lymph nodes, and other organs like the brain, liver, and bones. It is driven by cumulative lifetime genetic mutations caused by smoking and environmental toxins that lead to the universal inactivation of key tumor-suppression genes specifically TP53 and RB 1. The new combination treatment under study holds the promise for longer overall survival for patients with ES-SCLC.

Breaking from the #ESMO26 Presidential Symposium! 🚨 The Phase 3 DeLLphi-305 trial results mark a historic shift in first-line maintenance therapy for extensive-stage small cell lung cancer. https://t.co/TDx0n1P724

I always get excited by plenaries at major conferences. Today’s DeLLphi-305 results are an example of seeing the standard of care changing to better patients’ lives. Tarlatamab is finding its most exiting “moment” in MRD-low disease maintenance #ESMO26 #Tarlatamab

Median OS almost 2 years in ES-SCLC with Tarlatamab+Durvalumab maintenance = practice changing! ➡️ Challenge remains implementing Tarlatamab broadly + equitably so that all patients with ES-SCLC may benefit from this revolutionary therapy. @OncoAlert #ESMO26 @NEJM https://t.co/Ug6TxnAd1J

Proud to share that the primary analysis of the phase 3 DeLLphi-305 trial was presented today at #ESMO2026 in Madrid by Dr. Jacob Sands and simultaneously published in The New England Journal of Medicine. DeLLphi-305 evaluated tarlatamab plus durvalumab versus durvalumab alone as first-line maintenance therapy in extensive-stage small cell lung cancer, a disease where our patients urgently need better options. It is a true honor and a great joy to be part of the author group of this study, alongside such an outstanding international team of investigators. Above all, my gratitude goes to the patients and families who took part. I would also like to thank the Greek thoracic oncology community, which keeps making remarkable strides on the global stage, with a stronger presence at international congresses every single year. A heartfelt thank you to the clinical trials team of the 4th Oncology Department at the Interbalkan European Medical Center for their dedication and hard work behind every enrolled patient. And most of all, to my wife and co-PI, Dr. @ZairiEleni Eleni Zairi. Without her hard work, none of this would have been possible. #ESMO2026 #SCLC #LungCancer #ClinicalTrials #Oncology #NEJM #DeLLphi305

Pivotal #DeLLphi305 data @sands_jacob 👏, w/ a phenomenal discussion by @StephenVLiu w/ two standout quotes: ⭐️ "Innovation loses impact if it doesn't reach the patients who need it most" ⭐️ "It is not enough to know if the drugs work or how well they work, we need to know why and in whom they work to make better individualized decisions"

Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer https://t.co/ZLNLtmRQks

On Monday I told a patient with SCLC, this is the treatment plan today, but I’m hoping next week I can bring you better news from #ESMO26 👇 THIS is what we are here for! 🌟 PRACTICE CHANGING update for ES-SCLC: adding tarlatamb to maintenance durvalumab increases median OS by 58% (9mo) 🌟 Congrats to @sands_jacob and to all the DeLLphi-305 investigators! #ESMO26 #LCSM

Well-deserved standing ovation! The Phase 3 DeLLphi-305 trial showed that adding tarlatamab-dlle to durvalumab maintenance therapy significantly improved OS in lung cancer (ES-SCLC) patients without progression after initial chemoimmunotherapy. @myESMO @OncoAlert #bcsm #ESMO26 https://t.co/M7p8BFcHlo

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

💥Game-changer in small cell #lungcancer! #ESMO26 LBA3 DeLLphi-305: Tarlatamab + durvalumab vs durvalumab 1L maintenance in ES-SCLC (n=563) after chemo-IO. Median OS ⬆️ 21.1 vs 12.7 mo (HR 0.42), PFS ⬆️7.4 vs 1.9 mo (HR 0.34), ORR 26% vs 4%. ☢️44% of pts still on T+D due to #radiotherapy of oligoprogressive sites? #SCLC #LCSM @NEJM ➡️ https://t.co/nhVH10CQZG

🔥 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

DeLLphi-305. Immpresive curves . Additional Toxicity and cost in real world needs to be seen . Good for patients with extensive SCLC @myESMO @OncoAlert #esmo26 https://t.co/V2CDG9m0ZR

🔥 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

🆙#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 @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

🥊 ES-SCLC | THE POWER OF PARTNERSHIP! 2018: ATEZO opens the game! (IMpower133, OS HR 0.70) 2019: DURVA joins the fight! (CASPIAN, HR 0.73) 2025: ATEZO + LURBI enter maintenance! (IMforte, HR 0.73) 🔥 2026: DURVA + TARLA raise the stakes! (DeLLphi-305, HR 0.42) 🔮 NEXT: DeLLphi-312 takes TARLA into first line. Results awaited! 💡 A smart drug can change practice. The right partner, at the right time, can change the game! HRs reflect separate trials—not head-to-head comparisons. @myESMO @OncoAlert @larvol #ESMO26 #SCLC #Immunotherapy #Tarlatamab #MVOnco

🔥 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

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

#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 #melanoma vaccine trial shows the power of genetically tailored #cancer treatments: intismeran autogene, developed by @moderna_tx @Merck, show a significantly reduced risk of melanoma returning after surgery when combined with an existing #immunotherapy https://t.co/MM1wZ8xOSP https://t.co/ukFYD0RwKi

The benefit of cancer vaccine +pembrolizumab is equivalent to that of Herceptin (20 yrs ago- I was presnt in the audiotorium) - Inge marie Svane #ESMO2026 #INTERpath001 https://t.co/1pVhTptVZ5

DAY 2 — INTerpath-001 Individualised mRNA neoantigen therapy + pembrolizumab after melanoma resection improved 2-year RFS: 82.2% vs 70% (HR 0.58). A major proof of concept. OS is immature; manufacturing, cost and access are critical next questions. https://t.co/hbugKNO5C8

Encouraging news presented at the ESMO Congress 2026: in the phase 3 INTerpath-001 trial, adding a personalized mRNA-based cancer vaccine (intismeran autogene) to pembrolizumab after surgery reduced the risk of melanoma recurrence or death by 42%… https://t.co/FIcLoixNoz https://t.co/dGPwKzbrgU

Haber doğru, tam veriler de bu hafta ESMO 2026'da sunuldu. Yanlış anlaşılmasın diye mekanizmayı ve eksik kalan kısmı ekleyeyim Intismeran, melanomu ameliyatla alınmış hastaya nüksü önlemek için verilen bir tedavi Melanomda UV hasarı yüzünden tümör hücresinde çok sayıda mutasyon birikiyor. Bu mutasyonlar normal hücrede bulunmayan yeni protein parçaları üretiyor, bunlara neoantijen diyoruz Çıkarılan tümör dizileniyor, hastanın normal DNA'sıyla karşılaştırılıyor, bağışıklık sisteminin en iyi tanıyacağı 34'e kadar neoantijen seçiliyor Bunları kodlayan mRNA sadece o hasta için üretiliyor. Kas içine yapılıyor, hücre bu parçaları üretip bağışıklık sistemine gösteriyor, T hücreleri vücutta kalmış olası tümör hücrelerini tanımayı öğreniyor Pembrolizumab da T hücresinin üzerindeki PD-1 frenini kaldırıyor, ikisi birlikte veriliyor Rakamlar (INTerpath-001, Faz 3, evre IIB-IV melanom, 1137 hasta) Nüks ya da ölüm riski %42 azalmış (HR 0,58) 2 yılda nüksüz kalan oranı %70,0'dan %82,2'ye çıkmış Uzak metastaz ya da ölüm riski %38 azalmış (HR 0,62) 3. derece ve üstü tedaviye bağlı yan etki %14,2'ye %13,4, pembrolizumab tek başına verilenle neredeyse aynı Mekanizmayla çok uyumlu bir ayrıntı daha var İlk 6 ayda iki grup arasında fark yok (HR 0,99), fayda 6. aydan sonra ortaya çıkıyor (HR 0,42). T hücre yanıtının oturması zaman alıyor Eksik kısım genel sağkalım. Şu an HR 0,77 ama güven aralığı 0,45-1,31, anlamlılığa ulaşmadı, takip sürüyor Üretim tarafı da kolay sayılmaz. Taranan 1749 hastanın 302'si yeterli tümör örneği olmadığı için çalışmaya alınamadı, ameliyattan ilk doza kadar ortanca 64 gün geçiyor FDA değerlendirmesi de henüz bekleniyor Son olarak, aylardır "mRNA kanser yapar" diye yazan hesaplar bu çalışmayı nasıl açıklayacak merak ediyorum 757 hastaya mRNA verildi, kanserin geri dönme riski düştü ve ilacın kendisine bağlı tek bir ölüm olmadı Bunu turbo kanser anlatısının neresine koyacaklar??

I opened the paper behind your list (Kim et al., Biomarker Research 2025). The hazard ratios match. Let me explain, the way I'd explain it to a med student, why they can't carry the "mRNA turbo cancer" headline. 1. The same signal shows up without mRNA. The paper reports that cDNA vaccines, the adenovirus vector ones like AstraZeneca, were associated with higher thyroid, gastric, colorectal, lung and prostate cancer. mRNA was associated with thyroid, colorectal, lung and breast. Two platforms with completely different biology, almost the same list. A cause inside the mRNA vial can't explain a vaccine that has no mRNA in it. 2. The time window. Follow-up was 1 year. Lung, prostate, colorectal and breast cancers grow for years before they reach a size that can be diagnosed. A tumor diagnosed within months of a shot was most likely there before the shot. 3. Korea itself. Look at thyroid, the top HR on the list. Ahn, Kim and Welch showed in NEJM 2014 that Korea's thyroid cancer diagnosis rate in 2011 was 15 times the 1993 rate while thyroid cancer mortality stayed flat, more than 40,000 diagnoses a year against 300-400 deaths. That rise came from ultrasound screening. In a country where how often you're scanned decides how often thyroid cancer gets found, people who show up for vaccination are also the people who show up for checkups. More contact with the health system, more diagnoses. The database can't separate "more cancer" from "more cancer found." 4. Design. Retrospective insurance data. The authors don't claim causation. They write that further research is needed. And one more data point on mRNA and cancer, from a randomized trial this time. In INTerpath-001, 757 melanoma patients received a personalized mRNA therapy on top of pembrolizumab. Risk of recurrence or death fell by 42% versus pembrolizumab alone (HR 0.58). If mRNA drove cancer, how would it lower cancer recurrence in a randomized trial?

🧬 #ESMO26 INTerpath-001 (ph III): personalized mRNA vaccine intismeran + pembrolizumab in resected stage IIB–IV melanoma. 2y RFS 82.2% vs 70.0% (HR 0.58) DMFS HR 0.62 A milestone for mRNA vaccines; OS still immature. #melsm https://t.co/RXINDjjDlf

Intismeran autogene + Keytruda improves RFS and DMFS in melanoma patients, phase III INTerpath-001 trial finds https://t.co/G30MvYdXzF

For those interested in the details: Presented by Georgina Long at ESMO 2026 (LBA1, Presidential Symposium). Full paper in NEJM on Nov 11. Trial: INTerpath-001, 1,137 patients with resected stage IIB-IV melanoma, randomized 2:1. Benefit emerged after month 6 (HR 0.99 before, 0.42 after). 24-month RFS 82% vs 70%

📰Moderna publicó los resultados del ensayo de fase 3 INTerpath-001 En 1,137 pacientes cuyo melanoma se había extirpado, añadir intismeran (terapia personalizada de ARNm) a Keytruda redujo 42% el riesgo relativo de recaída o fallecer frente a solo Keytruda.

🧬 #ESMO2026 LBA1 · INTerpath-001: vacuna ARNm individualizada (intismeran) + pembro en melanoma resecado. RFS 82.2% vs 70.0% a 24 m (HR 0.58); DMFS 88.5% vs 80.2% (HR 0.62). EA G≥3 23.6% vs 20.3%. SG aún no reportada. 1.ª fase 3 positiva de vacuna ARNm. Reto: fabricación. #Melanoma #VacunaARNm

🎥 #OAOnTheGO | #ESMO26 Madrid @OncoAlert Personalized cancer vaccination is moving from concept to clinically meaningful signal. INTerpath-001 is positive. Dr. @MarioBalsaMD discusses pembrolizumab + personalized mRNA vaccine V940 in resected #Melanoma. 📊 2-year RFS: 82% vs 60% HR 0.58 📊 DMFS: 88.5% vs 80.2% HR 0.62 🎯 Why this matters: this is not simply another adjuvant immunotherapy study. It is a proof-of-concept that a patient-specific neoantigen vaccine can add meaningful disease-control benefit to PD-1 blockade. For me, the next questions are even more important: 🧬 Who benefits most? ⏳ Will this translate into an OS advantage? 🔄 How should it be positioned relative to neoadjuvant immunotherapy? 🎯 Can biomarkers identify the patients who truly need this degree of personalization? Excellent discussion by @MarioBalsaMD, building on important work from @ProfGLongMIA @jasonlukemd and the INTerpath-001 investigators. 🎬 Watch the latest #OAOnTheGO from @OncoAlert. @DrBetofMDPhD @cdanicas @UOzkerim @DrMirallas @DrYukselUrun @GaiaGriguolo @JankovicK @ElisaAgostinett @to_be_elizabeth @nataliagandur #OncoAlert #ESMO26 #Melanoma #mRNA #CancerVaccines #Immunotherapy #PrecisionOncology

Landmark #ESMO26 data from the phase 3 INTerpath-001 trial: intismeran autogene plus pembrolizumab reduced the risk of recurrence or death by 42% versus pembrolizumab alone in high-risk resected melanoma. The first positive phase 3 study of an individualized mRNA neoantigen therapy #melanoma @OncoAlert @myESMO

A huge step forward in personalised cancer care.Warmest congratulations to Professor Georgina Long and the entire INTerpath-001 team on these exciting phase III results presented at ESMO in Madrid. How is the vaccine personalised? Scientists compare the patient’s tumour DNA with their normal DNA to identify cancer-specific changes. These inform a bespoke mRNA vaccine encoding up to 34 tumour-specific targets, designed to help T cells recognise and attack that patient’s cancer. This is what makes these results so compelling: treatment designed around an individual cancer’s molecular signature, translating into meaningful clinical benefit. Eagerly awaiting the cardiac safety data in the full publication in @NEJM in November. @OncBrothers @HanCardiomd #ESMO26 #PersonalisedMedicine #CancerVaccines #Melanoma #PrecisionOncology #CardioOncology

Impressive results from INTerpath-001 #ESMO26 showing personalized mRNA vaccine works. Extraordinary tech but 17% did not have enough tissue for development. No increase in immune-tox and G5 were prior to mRNA. Not sure how this fits with NADINA & S1801. Cost will be a barrier. https://t.co/qJvgG5C0Q6

Which pave the way for the INTerpath-001 trial and its result. I believe his soul was there, watching that remarkable moment.

📌#OAOnTheGO 🎥 | OncoAlert at #ESMO26 Madrid INTerpath-001 is positive! 🔬 @ProfGLongMIA @jasonlukemd Dr. Mario Balsa (@HospitalClínic Barcelona) discusses pembrolizumab + personalized mRNA vaccine V940 in resected melanoma. 📊 2-year RFS: 82% vs 60% (HR 0.58) 📊 DMFS: 88.5% vs 80.2% (HR 0.62) Will this translate into longer survival? Who benefits most? And how does it fit with neoadjuvant immunotherapy? 🎬 Watch now!

It was a great honour to present the results of the phase 3 INTerpath-001 clinical trial at the #ESMO26 Congress in Madrid. This international trial included 1137 patients, across 157 sites, whose melanoma had been surgically removed, but who were at very high risk of it returning. The trial showed adding #intismeran autogene, an mRNA based individualised neoantigen therapy, to pembrolizumab reduced the risk of recurrence or death by 42%. This is the first phase 3 study to show that a treatment built from the unique ‘fingerprint’ of a patient’s own tumour can reduce the risk of recurrence or death from cancer. That fingerprint is read by sequencing the tumour, then a ‘wanted poster’ of the cancer is made as mRNA, showing the immune system exactly what to look for and attack. Having succeeded in melanoma, this proof of concept could mark the beginning of a foundational shift in how we treat cancer. Read more >https://t.co/quxTAFfntb A huge thank you to all patients and teams involved. @myESMO @Sydney_Uni @syd_health @Science_Academy @AAHMS_health @FulbrightAUS @NthSydHealth @ausoftheyear

WHAT IF THE NEXT CANCER VACCINE IS MADE FROM YOUR OWN TUMOR? CANCER VACCINES MAY HAVE JUST ENTERED A NEW ERA! At ESMO 2026 investigators presented Phase 3 results that could reshape how we prevent melanoma recurrence! The INTerpath 001 trial enrolled 1137 patients with surgically removed high risk melanoma! Researchers combined pembrolizumab with a personalized mRNA cancer vaccine called intismeran autogene! THE RESULTS ARE REMARKABLE! The relative risk of cancer recurrence or death fell by 42%! At two years 82.2% of patients receiving the combination remained recurrence free compared with 70% receiving pembrolizumab alone! The risk of distant metastasis or death also decreased by 38%! But the most extraordinary part may not be the numbers! IT IS THE BIOLOGY! Every cancer carries a unique collection of mutations! Some mutations produce abnormal proteins called neoantigens! These molecular abnormalities can distinguish malignant cells from healthy tissue! Investigators sequence the tumor and select up to 34 personalized neoantigens! They then manufacture an individualized mRNA therapy designed to teach the immune system to recognize those targets! Pembrolizumab helps release inhibitory brakes on T cells! The vaccine attempts to teach those cells exactly what to attack! Imagine treating cancer using a molecular fingerprint taken directly from the patient's own tumor! THIS IS NOT YET A CURE! Overall survival data remain immature! The vaccine remains investigational! Fever! Injection site reactions! Fatigue! Manufacturing time! And access must all be considered! BUT HERE IS WHERE I WOULD TAKE THE SCIENCE NEXT! Why wait until radiographic recurrence to discover that microscopic cancer survived? Could circulating tumor DNA identify patients harboring molecular residual disease? Could personalized vaccines be adapted when new resistant tumor clones emerge? Could T cell receptor sequencing reveal which neoantigens generate durable immune memory? Could we combine personalized vaccination with strategies that reverse T cell exhaustion? And perhaps most importantly! Could this approach extend beyond melanoma into pancreatic cancer! Lung cancer! And other malignancies with high recurrence rates? I would propose a prospective trial combining personalized neoantigen vaccination with serial circulating tumor DNA and longitudinal T cell profiling! We should test whether molecular clearance predicts durable remission and whether persistent molecular disease identifies patients needing additional treatment! The next frontier should not simply be treating visible cancer! It should be identifying and eliminating the microscopic disease that eventually causes relapse! Congratulations to Professor Georgina Long and the international INTerpath 001 investigators! The future of oncology may become increasingly individualized! ONE PATIENT! ONE TUMOR! ONE MOLECULAR FINGERPRINT! ONE IMMUNE SYSTEM TRAINED TO RECOGNIZE IT! Could personalized cancer vaccines eventually transform cancer from a disease we repeatedly treat into one we prevent from returning? Reference! ESMO 2026! INTerpath 001! Phase 3! NCT05933577! https://t.co/0RRJDimblK #ESMO26 #CancerVaccine #Melanoma #mRNA #Immunotherapy #PrecisionOncology

Georgina Long presented the positive phase 3 INTerpath-001 study of #intismeran -a personalised mRNA-based vaccine- combined with pembrolizumab in #adjuvant #melanoma at Presidential Symposium I at #ESMO26. #ESMOAmbassadors @myESMO https://t.co/fzYwh2xcOe

INTerpath-001: personalized mRNA therapy meets its primary RFS endpoint in resected stage IIB–IV melanoma. Intismeran + pembrolizumab vs placebo + pembrolizumab: 24-month RFS: 82.2% vs 70.0% HR 0.58; P<0.001 DMFS also improved. #INTerpath001 #ESMO2026 #Melanoma

🛡️The First Personalised mRNA Vaccine Shows Spectacular Results in Melanoma. Phase 3 INTerpath-001 trial evaluated the first-in-class personalised mRNA vaccine Intismeran autogene (mRNA-4157/V940) combined with Pembrolizumab in resected high-risk Stage IIB-IV melanoma. 📊RFS at 24 months was 82.2% vs 70.0% with pembrolizumab alone (HR 0.58; p<0.001). 📊42% reduction in the risk of recurrence or death. 💁INTerpath-001 sets a new benchmark for adjuvant therapy in melanoma. We are moving from "one-size-fits-all" treatments to individualised, bespoke immunotherapy

💯% agree Huge logistics and potential #GlobalOnc disparities for the deployment of a personalized adjuvant mRNA vaccine (intismeran autogene) INTerpath-001 trial for melanoma presented today at #ESMO26 “Lack of access to new treatments 🟰 unfulfilled promise” Maybe the market was reacting to this access challenge and not the magnitude of benefit❓#healthequity @GlopesMd

🧬 #ESMO26 | INTerpath-001: ¿nuevo paradigma en melanoma resecado? 💉 Vacuna personalizada + pembrolizumab: −42% de riesgo de recaída o muerte. 🔎 ¿Mejorará la supervivencia global? ¿Cómo integrar esta estrategia con la inmunoterapia neoadyuvante? #Melanoma #Immunotherapy https://t.co/qU4xMVOzK3

Promising data from #ESMO26 Presidential Symposium I: INTerpath-001 showed a 42% reduction in recurrence or death with individualized mRNA neoantigen therapy + pembrolizumab vs pembrolizumab alone in resected stage IIB–IV melanoma (HR 0.58; p<0.001). OS data remain immature. https://t.co/iSCh2TtNha

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

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 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

#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

🌟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

@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

@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

DAY 2 — VOLGA Perioperative enfortumab vedotin + durvalumab improved 2-year OS in cisplatin-ineligible/refusing muscle-invasive bladder cancer: 78.4% vs 69.4% (HR 0.58). Strong evidence, but more toxicity; no head-to-head comparison with other emerging regimens. https://t.co/kC7qsxBAI8

▸ ENZARAD: Enzalutamide added no MFS or OS benefit over older antiandrogen with ADT/RT ▸ VOLGA: perioperative durvalumab plus enfortumab vedotin improves EFS and OS in cisplatin-ineligible MIBC This evening on UrologyWatch, Oct 26: https://t.co/UQYtlKv0L7 https://t.co/XX59vtvjxX

Happy to have presented "Optimal induction treatment in non-metastatic bladder cancer" at #ESMO26 Madrid! Big thanks to the fantastic panel! @MichvdHeijden @giannatempopatr @LAUrology_NL Main message: deeper response = greater benefit. EV-based induction moves pCR most – and VOLGA suggests less EV may be enough! @OncoAlert @weoncologists @urotoday @Uromigos @OncoAlert and 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

*VOLGA study* cis-ineligible/refused @tompowles1 @MichvdHeijden @myESMO #ESMO26 @oncodaily @OncoAlert 🔴 EV+Durva x 3 w ⬆️ pCR, EFS, OS 🟠 ≈20% ❌ cystectomy 🟢 ct-DNA clearance associated w EFS 🔵 ⬆️ toxicity in triplet EV+Durva/T, will reduced dose impact oucomes? 🟣 Less migh be enough, more too much?

#ESMO26|#VOLGA ⭐️PhIII:PeriOp Durva ± Treme + NeoAdj EV vs control in cis-ineligible/refusing MIBC •Durva+EV: 2-yr EFS 64% vs 45% (HR 0.51); 2-yr OS 78% vs 69% (HR 0.58) •pCR 45% vs 10% •G3/4 TRAEs 30% (D+EV) vs 42% (+Treme) #BladderCancer #MIBC #bcsm #OncTwitter @tompowles1 https://t.co/TztSyVrHK9

#ESMO26 VOLGA (phase III, N=695): MIBC patients ineligible for or declining cisplatin. Perioperative durvalumab + neoadjuvant enfortumab vedotin vs radical cystectomy ± adjuvant therapy: 2-year EFS 64% vs 45% (HR 0.51); 2-year OS 78% vs 69% (HR 0.58; 95% CI: 0.40-0.83; p=0.0027).

Building on this thoughtful point I’d add another question: Can we separate the contribution of adjuvant EV from that of the immunotherapy backbone? VOLGA and KEYNOTE-905 differ in both EV duration and immunotherapy, so cross-trial comparisons cannot tell us who truly needs adjuvant EV. Could a randomized, ctDNA-guided trial help identify patients who can safely omit it? #VOLGA #ESMO26 #BladderCancer

9, 9, and 3. 💉 VOLGA out tonight in @NEJM — perioperative MIBC now has three winning EV regimens: EV-303: EV ×9 (3 pre + 6 post-cystectomy) → EFS HR 0.40 · OS HR 0.50 EV-304: EV ×9 (4 pre + 5 post) → EFS HR 0.53 · OS HR 0.65 VOLGA: EV ×3 — all preop, zero after surgery → EFS HR 0.51 · OS HR 0.58 ⅓ the vedotin. Most of the efficacy. 🧵 @myESMO @OncoAlert

Cisplatin-ineligible bladder cancer, VOLGA (ESMO 2026, NEJM): 3 cycles of enfortumab vedotin + durvalumab before cystectomy. 2-year survival 78% vs 69% with surgery straight away. The surgeon's fear with drugs-first is losing patients before theatre. 85% still reached cystectomy vs 78%. Delayed 4%, cancelled 0.9%.

And VOLGA. Looks v likely that we can optimise periop treatment in MIBC by reducing EV exposure. Lower neuropathy rates will be important for cured pts. On treatment QoL looks reassuring. Long term QoL data will be key 🧩 particularly given early impact of cystectomy @tompowles1 https://t.co/tkAIWZkb79

📌 An OncoAlert #Podium2Screen from the #ESMO26 Presidential Session Presented by our @OncoALert 🚨faculty @tompowles1 Perioperative Durvalumab ± Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 VOLGA Trial https://t.co/VVwsqDsk6h

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

🚨⭐🟠 #ESMO26 | Presidential Symposium | LBA2 | VOLGA Perioperative Durvalumab ± Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 VOLGA Trial 🎤 Presented by @tompowles1 🇬🇧 @OncoAlert @myESMO 🎬 Outstanding #Podium2Screen from our OncoAlert GU Faculty! 🔬 A major advance in curative-intent MIBC for patients ineligible for or declining cisplatin. 📊 PHASE III VOLGA | N=695 ✅ Durvalumab + EV vs control 📈 Event-free survival: • HR 0.51 (95% CI 0.38–0.67) • p<0.0001 • 2-year EFS: 64% vs 45% 📈 Overall survival: • HR 0.58 (95% CI 0.40–0.83) • p=0.0027 • 2-year OS: 78% vs 69% ✅ Pathological complete response: 45% vs 10% 🔬 Durvalumab + Tremelimumab + EV ✅ EFS HR 0.61 (95% CI 0.47–0.80) ⚠️ OS did not meet statistical significance at this interim analysis. ⚠️ Grade 3–4 treatment-related AEs: • Durvalumab + EV: 30% • Durvalumab + Tremelimumab + EV: 42% 📖 Simultaneously published in @NEJM! ⭐ MY POINT OF VIEW | CLINICAL PEARL VOLGA delivers what matters most in curative-intent oncology: improvement not only in pathological response, but also in event-free AND overall survival. 💡 The challenge now is determining how best to integrate EV-based perioperative strategies, optimize patient selection and minimize treatment-related toxicity. Importantly, VOLGA does not directly compare durvalumab + EV with pembrolizumab + EV. 🎯 The goal is not simply more intensive treatment, but more patients achieving long-term survival—and potentially cure. 👏 Congratulations to @tompowles1 and the entire VOLGA team on this landmark contribution! @urologysummit @gbanna74 @ravikanesvaran @Uromigos @LosUromigos @PGrivasMDPhD @apolo_andrea @AndreaNecchi @drenriquegrande @sonpavde @MattGalsky @montypal @DrChoueiri @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ #BladderCancer #MIBC #GUOncology #VOLGA #Immunotherapy #Podium2Screen

#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

🦉 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

Presidential Session ➡️ @NEJM ➡️ your screen. Our Amazing @OncoAlert faculty @tompowles1 🇬🇧breaks down VOLGA: perioperative durva + neoadjuvant EV improves EFS and OS in cisplatin-ineligible MIBC. Kudos to Dr. Powles and team on the great trial, presentation and NEJM publication A must-watch 🎥👇 #ESMO26 #Podium2Screen #BladderCancer

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

@tompowles1 with #VOLGA phase 3 of EV-durva, EV-tremi-durva, vs cystectomy. EV-durva improved EFS & OS. Great to see survival improved w neoadj doublet. Triplet misses partly due to tox. Pub’d in @NEJM today. We were pleased to treat pts on VOLGA @utswcancer @OncoAlert #ESMO26 https://t.co/TSXdZ74BOc

#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

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

The #ESMO26 Presidential Symposium is about to begin! 🔥 Super excited to hear the highly anticipated results of the VOLGA trial, presented by the the only and only @tompowles1! @myESMO @apolo_andrea @Uromigos @brian_rini @OncoAlert @LosUromigos @uromigosjapan @MichvdHeijden

#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

💔 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

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

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

Divarasib as Compared with Sotorasib or Adagrasib in KRASG12C–Mutated NSCLC https://t.co/hgK0FILNr6 Quoting the great @DavidHongMD - First in class is not always the best in class. We will keep seeing this more often. #ESMO26

DAY 3 — Krascendo 1 In previously treated KRAS G12C NSCLC, divarasib beat sotorasib/adagrasib: OS 17.7 vs 12.0 months (HR 0.56). A rare survival gain versus active targeted comparators. Follow-up is relatively short, and untreated brain metastases were excluded. https://t.co/k2nsx0Gedt

3. KRASCENDO-1 Divarasib Vs sotorasib or adagrasib, previously treated disease. OS 17.7m vs 12m. New SoC. NEJM 4. OptiTROP-Lung06 Sacituzumab tirumotecan + pembrolizumab in Chinese 1st line nonsquamNSCLC, PD-L1 <1%, without EGFR/ALK alterations. PFS 15m vs 5.7m. NEJM #ESMO26 https://t.co/OzWni3cnEZ

🫁 #ESMO26 KRASCENDO-1 (ph III): divarasib beat sotorasib/adagrasib head-to-head in pretreated KRAS G12C NSCLC. PFS 9.8 vs 5.7 mo (HR 0.58) OS 17.7 vs 12.0 mo (HR 0.56) ORR 58% vs 32% Potential new benchmark; 91% of controls got sotorasib. #lcsm https://t.co/nxxYRnwn7F

🔥Lung🫁 #ESMO26 #LCSM 🎉Again🔂 4⃣ @NEJM 🎯DeLLphi-305 🎯OptiTROP-Lung06 🎯Krascendo 1 🎯SAFFRON 2⃣ @TheLancet 🎯PANKU-Lung01 🎯HERON-Lung01 3⃣ @Annals_Oncology 🎯PERSEE 🎯DeLLphi-304 🎯NEOTORCH 1⃣ @Nature 🎯NeoCOAST-2 1⃣ @NatureMedicine 🎯MDT-BRIDGE 1⃣ @JCO_ASCO 🎯Dalmelitinib Plus Aumolertinib @OncoAlert @Larvol @myESMO @IASLC @ASCO @EGFRResisters @KRASKickers @metcrusaders

A new standard of care arrives in advanced KRAS G12C NSCLC: Divarasib (Krascendo-1) 🔸 Global, randomised, phase 3 🔸 Compared to current KRASi (mainly sotorasib) 🔺 No cross-over What do we know so far? 🔹 2L sotorasib or adagrasib show modest PFS benefit vs docetaxel, but no OS benefit What did we see at #ESMO26? ✅ Improved PFS, 9.8 v 4.7m: HR 0.58 ✅ Improved ORR, 58% v 32% ✅ Improved OS, 17.7m v 12m: HR 0.56 ⚠️ Lower Gr3+ AEs, but more Gr1-2 AEs - especially GI What does this mean? ❗️New standard of care for KRAS G12C ✅ Clearly superior to current options 🤔 Need QoL & PRO data 🤔 Need intra-cranial activity data ⚠️ Side effects remain an issue, albeit lower grade (Gr2 diarrhoea is still pretty miserable) ❗️Drug access will be the main issue, especially with Sotorasib withdrawal of funding in many countries 🤔 1L, in combination with other agents, likely to be ultimate place for this drug #LCSM

📍 Krascendo 1 🫁 #krasg12c #nsclc #esmo2026 #presidentialSymposium2 Phase 3, global, randomised trial of divarasib vs sotorasib or adagrasib in advanced/metastatic KRAS G12C-mutated NSCLC. 🍁Results🍀 -A significant benefit in PFS (HR: 0.58; 95% CI: 0.44–0.76), 9.8 vs 5.7 months for diva vs soto/ ada . -A significant benefit in OS (HR: 0.56; 95% CI: 0.41–0.78) , 17.7 vs 11 months for diva vs soto/ ada -A significant improvement in ORR was seen for diva (58.4%) vs soto/ ada (32.3%) @myESMO @HemOncFellows @IMG_Oncologists @hemeoncfellow

🚨#ESMO26 and last but not least Top Lung Abstract goes to the new Diva 💃 of #KRASG12C #lungcancer! #KRASCENDO1: Phase III #Divarasib vs sotorasib/adagrasib after prior chemotherapy for #KRASG12C NSCLC 📈 PFS: 9.8 vs 5.7 mo (HR 0.58) 🔥 OS: ~18 vs 12 mo (HR 0.56) 🎯 ORR: 58.4% vs 32.3% ⚠️ Grade 3–4 TRAEs: 24.6% vs 34.5% 🏆This is clearly practice changing with a much better tolerated drug and fewer side effects ( although still GI toxicity) compared to current standard for this high-risk population. 🤔Still some questions about exclusion of untreated brain mets and low number of adagrasib treated pts in control arm #lcsm @KRASKickers

🚨 #ESMO26 | Phase III KRAScendo 1 demonstrates a major advance in previously treated KRAS G12C-mutant NSCLC. Compared with sotorasib/adagrasib, divarasib reduced the hazard of death by 44% (HR 0.56), extending median overall survival from 12.0 to 17.7 months. The hazard of progression or death decreased by 42% (HR 0.58), with median progression-free survival improving from 5.7 to 9.8 months. Objective responses increased from 32% to 58%, while grade ≥3 treatment-related adverse events decreased from 35% to 25%. These findings establish strong evidence for next-generation KRAS G12C inhibition as a potential new treatment standard. #LBA5 #LungCancer

KRAScendo-1 #ESMO26 shows divarasib (more potent iKRAS-G12C) > sotorasib/adagrasib for PFS/OS. Active drug and new SOC IMO in this group. Whilst G3 AE lower with div, seems to be mainly driven by less transaminitis. GI tox is higher and proactive rather than reactive Rx is key.

KRAScendo 1: divarasib met its primary PFS endpoint and improved OS vs a sotorasib-dominant control. OS: 17.7 vs 12.0 mo; HR 0.56. Is OS now the benchmark for next-generation KRAS G12C inhibitors? https://t.co/kge3fOW58B @FSkoulidis @myESMO @OncoAlert @OncoDaily #ESMO26

Day 3 (Presidential II) #ESMO26 highlights: 1. Krascendo-1: Divarasib in KRAS G12C NSCLC 2. SAFFRON: Osi + Savolitinib in EGFRm/MET+ NSCLC 3. CLARITY-Gastric01: Sone-Ve CLDN18.2 ADC in Gastric 4. HARMONi-GI1: Ivo + Chemo in 1L BTC 1/5 #OncTwitter #lcsm #gism @myESMO https://t.co/HCh0uT89j7

Divarasib beats adagrasib and sotorasib in the 2nd line treatment of KRAS G12C mutated NSCLC. This sets a new standard for now, but I’m hopeful that this is just the first of many positive trials in KRAS mutated NSCLC in the coming years. @KRASKickers @myESMO #ESMO26 https://t.co/DmGmetbUuz

KRASCENDO-1: divarasib vs sotorasib or adagrasib in previously treated KRAS G12C advanced NSCLC (n=338). Primary endpoint (PFS by BICR): 9.8 vs 5.7 mo, HR 0.58 (95% CI 0.44–0.76). OS: 17.7 vs 12.0 mo, HR 0.56 (95% CI 0.41–0.78), significant at preplanned interim analysis. Grade 3–4 treatment-related AEs: 24.6% vs 34.5% #ESMO26 #LCSM #OncTwitter @BenjaminBesseMD @Alfdoc2 @HHorinouchi @DrSanjayPopat @OncoAlert

Two more #ESMO26 papers in @NEJM today: In EGFR-mutated, MET-altered NSCLC progressing on osimertinib, adding savolitinib improved PFS (HR 0.55) and OS (HR 0.68) vs platinum-pemetrexed. 12-month OS was 70% vs 53%. In previously treated KRAS G12C-mutated NSCLC, divarasib improved median PFS (9.8 vs 5.7 months; HR 0.58) and OS (17.7 vs 12.0 months; HR 0.56) vs sotorasib or adagrasib.

🚨🫁 ESMO26 | KRASCENDO-1 – Fase III Divarasibe vs. sotorasibe/adagrasibe no CPNPC avançado KRAS G12C mutado, previamente tratado. ✅ Sobrevida global: 17,7 vs. 12,0 meses (HR 0,56) ✅ 44% de redução no risco de morte ✅ PFS: 9,8 vs. 5,7 meses (HR 0,58) ✅ Resposta objetiva: 58% vs. 32% ✅ Menos eventos adversos relacionados ao tratamento de grau 3–4: 24,6% vs. 34,5%. 🎯 Potencial novo padrão de tratamento, com ganho significativo de sobrevida e melhor perfil de segurança. #ESMO26 #KRASCENDO1 #Divarasib #KRASG12C #LungCancer

Exciting! Great to have participated in the phase 1 trial G042144 of divarasib led by @RashaCosman from #SVHA and see its phase 3 success at #ESMO26 https://t.co/LSVXkvDeeA

Roche's divarasib cut death risk 44% vs sotorasib/adagrasib in previously treated KRAS G12C lung cancer at ESMO, with median survival about 18 vs 12 months. A head-to-head Phase 3 win like this should reset the KRAS standard — watch for the FDA filing next.

Brilliant discussion from Dr. @BenjaminBesseMD at #ESMO26 on the Krascendo 1 study of divarasib vs sotorasib/adagrasib. Rightly points out lack of crossover in a study with a PFS endpoint as unjust. Excellent points all around. #ESMOAmbassadors https://t.co/AZp29NMYLI

🚨 Exciting results from #ESMO26! Phase III KRAScendo-1: Divarasib outperformed sotorasib/adagrasib in KRAS G12C-mutated NSCLC. 🔹 PFS: 9.8 vs 5.7 months 🔹 OS: 17.7 vs 12.0 months 🔹 ORR: 58% vs 32% Better efficacy with fewer grade ≥3 treatment-related adverse events! Could divarasib become the new standard of care? 👀 @OncoAlert @weoncologists @StephenVLiu @GlopesMd @OpenMedKate @ManuelDomine

🔥 KRASCENDO-1 at #ESMO26: @BenjaminBesseMD takes the stage! As usual, a provocative, funny, and absolutely captivating discussion Following the impressive PFS and OS results with divarasib, Benjamin challenged us to think beyond the numbers. 🎯 Key messages: 🔹 Divarasib demonstrates clear superiority over sotorasib/adagrasib, including a meaningful OS benefit. 🔹 Is this the farewell tour for first-generation KRAS G12C inhibitors? 🎸 🔹 The next frontier: moving KRAS G12C inhibition into first-line combinations with immunotherapy ± chemotherapy. 🔹 Clinical trials must evolve: reconsider crossover, better capture chronic toxicity, and broaden eligibility to reflect real-world patients. My take: Great science deserves great discussions. @BenjaminBesseMD once again managed to combine sharp scientific criticism, humour, and a clear message ! 👏 #ESMOAmbassadors #ESMO26 #KRASG12C #Divarasib #NSCLC #LungCancer

🫁 #ESMO26 Krascendo 1 (ph III): divarasib beats soto/ada head-to-head in 2L+ KRAS G12C NSCLC PFS 9.8 vs 5.7 mo (HR 0.58) OS 17.7 vs 12.0 mo (HR 0.56) ORR 58% vs 32% Likely new 2L SoC. Caveats: control 91% sotorasib, immature OS, GI tox (diarrhea ~60% in ph I). https://t.co/s0i4iosvF0

Impressive results: KRASCENDO-1 Phase III Divarasib vs. Sotorasib vs. Adagrasib (N= 338) for KRAS #G12C MT #NSCLC #lungcancer 🫁 - 30% had a history of treated brain met - majority had received Sotorasib 🔹Primary PFS: 9.8 vs. 5.7M; HR = 0.58 🔹Secondary OS: 17.7M vs. 12M (HR = 0.56) 🔹ORR: 58% vs. 32% #cancerresearch @OncoAlert #cancer @Roche #ESMO2026

#ESMO26 From Dr. Benjamin Besse’s excellent discussion of KRASCENDO-1 👏👏👏 https://t.co/v7cdYOjSN7

📣 Second Presidential Symposium #ESMO26 KRASCENDO-1: Divarasib vs Sotorasib/Adagrasib in 1-3L #KRASG12C #NSCLC 📌 PFS 9.8 vs 5.7m HR 0.58 📌 OS 17.7 vs 12m HR 0.56 ☣️ Diarrhea (66%), N/V (53/39%) @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @NEJM @brunolarvol 👇🏽👇🏽 https://t.co/M21g3ISLPv

Krascendo 1 met its endpoint of divarasib vs sotorasib/adagrasib in previously treated KRAS G12C NSCLC 🫁 ✅ mPFS 9.8 vs 5.7m HR 0.58 ✅ mOS 17.7 vs 12.0m HR 0.56 ✅ ORR 58% vs 32% 🌟Well tolerated with mostly G1/2 diarrhoea, N+V ❌ Crossover not allowed 😢 Await 1L studies in with Krascendo 170 & 2 Congrats to @FSkoulidis and co investigators 👏🏼👏🏼👏🏼 @Roche Great discussant @BenjaminBesseMD and well said 💪🏼 🙏🏼 Access is key now - we need it for our patients. #PresidentialDay2 #ESMO26 @myESMO

A new second-line standard of care for KRAS G12C-mutant NSCLC? KRASCENDO-1: Divarasib significantly improved PFS, OS and ORR versus sotorasib/adagrasib, with fewer severe treatment-related adverse events. A potentially practice-changing Phase III trial. #ESMO26 #KRASG12C #LungCancer

The results are in: 17.7 months median survival versus 12.0. Risk of death cut by 44%. Divarasib is the first in this class to show people actually survive metastatic lung cancer longer. Which is remarkable. When sotorasib was tested against chemotherapy, survival was no different. That's not unusual. Plenty of cancer drugs reach the market without proving they extend life, only that scans look better for longer. The gamble didn't just find a better drug. It found the first one clearing a bar everyone assumed was already being cleared. Another very impressive chapter in the KRAS story across different diseases.

✨ PRACTICE CHANGING ✨ data from #ESMO26 Divarasib becomes the NEW Standard of Care for 2L KRAS G12C #LungCancer @FSkoulidis presents results from Krascendo 1 Divarasib significantly prolongs PFS and OS with a more tolerable safety profile https://t.co/JAcDUqlyDi

#ESMO26 At the Presidential Session, the KRASCENDO-1 discussant seems to be getting more applause than the actual study presentation. Quite telling, isn't it? I wonder why… 🤔 @SuyogCancer

@bensolomon1 @FSkoulidis Congrats Krascendo team - amazing results

New standard of care for KRAS G12C mutation positive NSCLC. @FSkoulidis presents Krascendo-1 head to head trial of divarasib vs sotorasib or adagrasib- convincing improving PFS (9.8 m vs 5.7 m, HR 0.58) and OS (17.7m vs 12.0m, HR 0.58) https://t.co/6sxEHeDjAq

KRaSCENDO Trial. Excellent results comparing Divarasib (anext generation KRAS inhibitor) with sotorasib showing a clear benefit in PFS, OS, with rapid and durable responses. @oncoalert @myesmo #ESMO2026 MADRID @Hospital_FJD @quironsalud #LCSM https://t.co/GhS7Nc4mt3

Certainly we are hearing a crescendo in the activity of K-Ras G12C targeting agents based on great presentation by Dr. Skoulidis! The new diva of our K-Ras field, divarasib clealy is superior as to efficacy as compared to adagrasib/sotorasib based on Krascendo-01. PFS HR of 0.58/4 month abs difference plus OS HR of 0.56/6 m median OS delta. And in addition, surprisingly for a diva it actually needs less maintenance than ada/soto (only 5% treatment discontinuation rate) so a true win-win! No prokrastination needed- a new SOC targeted agent and hopefully one that could move up to frontline/ periop and other avenues as well!

Practice-changing KRAS G12C data! @Fskoulidis presents Krascendo 1 Ph.III: divarasib vs sotorasib/adagrasib in pretreated NSCLC. PFS 9.8 vs 5.7 mo (HR 0.58; p<0.0001). OS 17.7 vs 12.0 mo (HR 0.56; p=0.0005). ORR 58% vs 32%. #ESMO26 #LungCancer @myESMO @OncoAlert https://t.co/eAk2Th9t3a

Divarasib is improving the existing data in PFS , OS and ORR in KRAS G12C NSCLC in the Krascendo 1 trial. A really good news for our patients! Congrats @FSkoulidis & team! Simultaneous publication in @NEJM Excellent discussion @BenjaminBesseMD @KRASKickers @myESMO #ESMO26 https://t.co/trgiiEnUeQ

KRASCENDO trial: Divarasib a second generation KRAS G12C inhibitor improves PFS and OS in mNSCLC compared to 1st Generation sotorasib. #ESMO2026 @curijoey @myESMO @darioT_ @OncBrothers https://t.co/M6ftebVF1b

Presidential Session: Krascendo 1: Next-generation KRAS G12C inhibition delivers. Divarasib vs sotorasib/adagrasib in previously treated advanced NSCLC: • PFS: 9.8 vs 5.7 mo (HR 0.58) • OS: 17.7 vs 12.0 mo (HR 0.56) • ORR: 58% vs 32% Compelling head-to-head evidence! #LCSM @myESMO #ESMO26 @Larvol @OncoAlert

A new SoC enters the #KRASG12C room breaking down the door! Divarasib improves both PFS and OS vs Sotorasib/Adagrasib #ESMO26 #ESMOAmbassadors @FSkoulidis https://t.co/V222cYE1Pj

🔥🚨@OncoAlert Hot off the press. Just published @NEJM in conjunction with presentation @myESMO #ESMO26 results of: ⭐️#KRASCENDO-1 phase 3 trial of: ❇️#Divarasib Vs #Sotorasib/or #Adagrasib 🎯For #PreviouslyTreated #KRAS (#G12C)+ advanced non-small-cell #LungCancer (#NSCLC). Study showed: ‼️Statistically significant & clinically meaningful ⬆️#ProgressionFreeSurvival (primary endpoint) & #OverallSurvival Benefits. ✅#mPFS: 9.8 vs 5.7 months (HR 0.58) ✅#mOS: 17.7 vs 12.0 months (HR 0.56) ✅#ORR: 58.4% vs 32.3% ✅ ⚠️ Grade ≥3 AEs: 24.6% vs 34.5% 👇🏻 https://t.co/6ggEpQD0vW

💊 Sotorasib and adagrasib were fundamental proof of concept drugs approved for a clear unmet need even none of them never demonstrated overall survival benefit. 🤯 Today those drugs are part of the past in oncology history. Divarasib improve ORR, PFS and OS in previously treated KRAS G12C mutant NSCLC with a better safety profile in Krascendo1 Ph3 randomized clinical trial. Kudos to @Roche to conduct a F2F trial. #ESMO26 #LCSM

🔥🔥Krascendo-1: divarasib vs 1st-gen #KRAS G12C inhibitors in pretreated #NSCLC (n=338), in @NEJM ➡️ mPFS 9.8 vs 5.7 mo | HR 0.58
➡️ mOS 17.7 vs 12.0 mo | HR 0.56
➡️ ORR 58% vs 32%
➡️ Discontinuation for TRAEs 4.8% vs 11.7% 🎯 It beats the first drugs to land in KRAS G12C, and it does so on OS. Neither had shown an OS benefit over docetaxel. 🔍 The control arm was 91% sotorasib. New 2L standard, though still far from what other oncogene-driven NSCLC gets with targeted therapy. @KolPulseAI @OncoAlert @myESMO @_SEOM @KRASKickers #ESMO26

SCRI/WVCI enrolled 10-15% of the total North American population to this positive global study for lung cancer. Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C–Mutated NSCLC | New England Journal of Medicine https://t.co/Lh8ey0cKY6 @OncoAlert

KRASCENDO 1: diva v soto/adag; off inhibitor; pretreated; n338: PFS HR 0.58; 4.1m longer mPFS; OS HR 0.56; 5.7m longer OS; mDOR 11.9m ORR 58%; CNS activity not as deep; #ESMO26 @BTOGORG https://t.co/CeUxEq2rFg

Proud to contribute to the Phase III Krascendo 1 study, presented at #ESMO2026 and published in @NEJM. Co-author @BoWangMD1 called the findings “potentially practice-changing” for patients with KRAS G12C-mutated lung cancer. https://t.co/Qz6C2ERZGr

Two highly anticipated studies will be presented at today's Presidential Symposium #ESMO26 ① KRASCENDO-1: Results from a head-to-head trial comparing two KRAS inhibitors in patients with KRAS G12C-mutated NSCLC

@M_Torasawa Good to finally see a head-to-head G12C trial. Twice the time on treatment with fewer grade 3-4 events fits with divarasib being far more potent in the lab. Keen to see whether the benefit holds in the KEAP1 co-mutant patients, who did badly on the first-gen drugs.

🫁#ESMO26 I Divarasib reduce el riesgo de muerte un 44% en cáncer de #pulmón con KRAS G12C frente a las terapias actuales. 👉🏻Con el fármaco de @Roche_es la mediana de supervivencia global fue de 17,7 meses con divarasib, frente a 12,0 meses con Sotor... https://t.co/BIRbWtNwwe

4 studies I’m watching today at #ESMO26 Presidential Symposium II (16:30 CET): KRAScendo 1, SAFFRON, CLARITY-Gastric 01 and HARMONi-GI1. Which one are you waiting for? I’ll post notes right after each LBA. #Oncology https://t.co/2qVqWcF773

ESMO 2026 presidential 2 | KRASCENDO-1: Phase III trial (n=338): Divarasib vs sotorasib/adagrasib in previously treated advanced NSCLC. 📊 Impressive results: ✅ mPFS: 9.8 vs 5.7 months (HR 0.58; p<0.0001) ✅ mOS: 17.7 vs 12.0 months (HR 0.56; p=0.0005) ✅ ORR: 58.4% vs 32.3% ✅ Grade 3–4 TRAEs: 24.6% vs 34.5% ✅ TRAEs leading to discontinuation: 4.8% vs 11.7% 🔥 A 44% relative reduction in risk of death, with better response rates and tolerability! @OncoAlert @myESMO #ESMO26 #LungCancer #KRAS #Oncology

🌟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

DAY 3 — SAFFRON After osimertinib progression in EGFR-mutant/MET-altered NSCLC, osimertinib + savolitinib improved OS vs platinum–pemetrexed: 17.8 vs 12.9 months (HR 0.68). Repeat biomarker testing matters. Toxicity and comparisons with newer strategies remain key. https://t.co/ofbl6uhSFy

MET targeting in EGFRm NSCLC: 3 trials, distinct settings. SANOVO (1L, MET-OE): PFS HR 0.56; p<0.0001 SAFFRON (post-osi, MET-OE/amp): HR 0.55; p<0.001 Dalmelitinib + aumolertinib (post-TKI, MET-amp): HR 0.60; p<0.001 Not head-to-head. @StephenVLiu @OncoAlert @OncoDaily #ESMO26

Changes soon (NICE/CDF pending) 1. DeLLphi-305 Tarlatamab + durvalumab as first-line maintenance in SCLC. New SoC. median OS 21.1m vs 12.7m. NEJM 2. SAFFRON Osimertinib + savolitinib new SoC after osimertinib progression with MET driven resistance. OS 17.8m Vs 12.9. NEJM #ESMO26 https://t.co/noByEiHPva

A lot of new data on 2L post-EGFR TKI NSCLC treatment options in #ESMO26. What can we make of it all? OptiTROP-Lung04: 👉 Sacituzumab-TMT (TROP2 ADC) vs. chemo 🔹 China-only, Ph3, randomised, open-label ✅ Previously positive PFS (ESMO 2025) ✅ Improved OS, 25.9 v 17.4m: HR 0.69 ⚠️ Similar TRAEs, slightly more Gr1-2 with Saci-TMT SAFFRON: 👉 Adding Savolitinib to Osimertinib in MET over-expressing (OE) / amplified 🔹 Global, Ph3, randomised v chemo ✅ Improves mPFS 7.6m v 5.4m: HR 0.55 ✅ Similar benefit for OE & amplified pts ✅ Improved OS 17.8m v 12.9m: HR 0.68 ⚠️ Lower Gr3+ AEs (40% v 52%) but higher Gr1-2 toxicity - oedema as expected PANKU-Lung01: 👉 Iza-Bren (EGFR x HER3 ADC) v chemo 🔹 China-only, Ph3, randomised ✅ Improved mPFS 11.7 v 5.7m: HR 0.40 ✅ Improved ORR 60% v 34% ❓OS, immature ⚠️ Higher Gr3+ AEs (78% v 62%). Mainly myelosupression ⚠️ High dose interruption (53%) & reduction (60%) ⚠️ Needs GCSF prophylaxis HERON-Lung01: 👉 Rus-Rez (HER3 ADC) v chemo 🔹 China-only, Ph3, randomised ✅ Improves mPFS, 8.3m v 5.4m: HR 0.47 ❓OS, immature ⚠️ Similar Gr3+ TRAEs, but higher Gr-2 AEs. Mainly myelosupression …and add to this current / other options: 🔸 Pemetrexed & carboplatin 🔸 COMPEL: Osimertinib + chemo 🔸 MARIPOSA-2: Amivantamab + chemo 🔸 HARMONi: Ivonescimab + chemo 🤯 So, how do we interpret this? 🤔 Extraordinary proliferation of 2L options. Impossible to know today which is best 🤔 China-only studies needs global validation, as EGFR population different to rest of world 🤔 A biomarker driven option (SAFFRON) appealing, although only minority of patients MET OE/amp 🤔 Arrival of active ADCs very welcome, but biomarkers needed to better select patients 🤔 ADCs not necessarily less toxic than chemo: perhaps no increase in Gr3+, but a lot of Gr1-2 AEs 🤔 What is available 2L will impact on what we choose in 1L. In turn, what we choose 1L may impact on what we can use 2L (e.g. different MET alterations with Ami/Laz) Conclusions: hugely complex. Only answerable with longer follow up & global studies. #LCSM

מה עושים כשהגידול מתקדם לאחר טיפול בטגריסו? כיצד ניתן לתקוף את מנגנון העמידות שלו? סקירה של מחקרי SAFFRON, SANOVO מכנס #ESMO2026 #ESMO26 והשווה למחקר MARIPOSA-2 הקודם: אחד ממנגנוני העמידות המרכזיים שמפתחים בחולי NSCLC עם מוטציית EGFR תחת טיפול בטגריסו הוא הפעלה של מסלול MET זיהוי מדויק של מנגנון זה מאפשר היום לשקול טיפול ממוקד במקום מעבר לכימותרפיה 1. מחקר SAFFRON טיפול ממוקד לאחר התקדמות על בטגריסו במחקר פאזה III הגלובלי SAFFRON הושווה השילוב osimertinib + savolitinib לכימותרפיה מבוססת פלטינום ואלימטה, בחולים עם NSCLC מתקדם הנושא מוטציית EGFR, שמחלתם התקדמה לאחר osimertinib ושבגידולם נמצא ביטוי־יתר משמעותי של MET ו/או הגברה של הגן MET. התוצאות המרכזיות: - mPFS: 7.6 לעומת 5.4 חודשים; HR 0.55 - mOS: 17.8 לעומת 12.9 חודשים; HR 0.68 - ORR: 51% לעומת 27% - הישרדות לאחר שנה: 70% לעומת 53% היתרון היה מובהק סטטיסטית הן ב־PFS והן ב־OS. זהו ממצא משמעותי, משום שמדובר במחקר פאזה III גלובלי שהדגים תועלת בשני מדדים אלה באוכלוסייה שנבחרה על בסיס מנגנון עמידות מוגדר. בנוסף, מדובר בשילוב פומי, מה שעשוי להיות יתרון מבחינת נוחות הטיפול. 2. איך SAFFRON משתווה ל־MARIPOSA-2? מחקר MARIPOSA-2 הוא מחקר פאזה III שבחן גישה אחרת לאחר התקדמות על טגריסו הוספת amivantamab (נוגדן דו־ספציפי המכוון ל־EGFR ול־MET) לכימותרפיה מבוססת carboplatin ו־pemetrexed. בניגוד ל־SAFFRON, המחקר לא הגביל את ההשתתפות לחולים עם ביטוי־יתר או הגברה של MET, אלא כלל חולים עם מוטציות EGFR שכיחות (בעיקר exon 19 deletion ו־L858R). בזרוע amivantamab + כימותרפיה, לעומת כימותרפיה בלבד: - mPFS: 6.3 לעומת 4.2 חודשים; HR 0.48 - ORR: 64% לעומת 36% - mOS: 17.7 לעומת 15.3 חודשים; HR 0.73 חשוב לדייק לגבי ההישרדות הכוללת: בניתוח הביניים השני התקבל p=0.039, אך התוצאה לא עברה את סף המובהקות הסטטיסטית שהוגדר מראש. לכן אין להציג את יתרון ה־OS כיתרון מובהק לפי תכנון המחקר. בזרוע נפרדת נבחן גם שילוב amivantamab + lazertinib + כימותרפיה (mPFS 8.3 מול 4.2 חודשים, HR 0.44), אך יש להביא בחשבון את פרופיל הרעילות של המשטר המשולש. ההבדל הקליני בין המחקרים מחקר SAFFRON מתמקד באוכלוסייה נבחרת שבה הודגם מנגנון עמידות הקשור ל־MET, ובוחן שתי תרופות ממוקדות הניתנות דרך הפה. MARIPOSA-2 מציע אפשרות רחבה יותר לאחר osimertinib, ללא צורך בבחירת חולים על בסיס MET, אך כולל טיפול תוך־ורידי עם פרופיל רעילות שונה. 3. SANOVO האם נכון לחסום EGFR ו־MET כבר בקו הראשון? מחקר SANOVO בחן האם יש יתרון להתערבות מוקדמת, עוד לפני הופעת עמידות ל־osimertinib. במחקר פאזה III שנערך בסין נכללו חולים שטרם טופלו במחלתם המתקדמת, עם מוטציית EGFR וביטוי־יתר של MET (IHC 2+ או 3+). המשתתפים קיבלו טגירסו + savolitinib או טגריסו בלבד. התוצאות שהוצגו ב־ESMO 2026: - באוכלוסייה הכוללת: mPFS 24.9 לעומת 13.8 חודשים; HR 0.56 - בתת־הקבוצה עם IHC 3+ גבוה: mPFS 24.8 לעומת 11.1 חודשים; HR 0.45 - ב־OS דווח HR של 0.48, עם חציון OS של 44.5 לעומת 34.9 חודשים אלה נתונים מעודדים, התומכים באפשרות של חסימה כפולה ומוקדמת בחולים שנבחרו לפי ביומרקר. עם זאת, SANOVO נערך בסין והשווה את השילוב ל־osimertinib בלבד. בהקשר הרחב יותר של קו ראשון כבר קיימות אפשרויות שילוב אחרות (כמו osimertinib + כימותרפיה ב־FLAURA2 או amivantamab + lazertinib ב־MARIPOSA), ולכן נדרשת בחינה נוספת של מקומו בפרדיגמה הטיפולית. *חשוב לזכור שביטוי־יתר של MET לפי IHC והגברה של הגן MET אינם ממצאים זהים, ויש להתייחס לספי ההגדרה ולשיטות הבדיקה שבהן השתמש כל מחקר. בשורה התחתונה: האתגר הקליני כעת הוא לא רק להוסיף עוד טיפולים יעילים, אלא להתאים לכל מטופל את הגישה המתאימה לפי סטטוס MET, קו הטיפול, פרופיל הרעילות, נוחות הטיפול והזמינות🙏

SAFFRON #ESMO26: osi+savo vs platinum-pem post-osimertinib, EGFRm MET OE/amp NSCLC ➡️ mPFS 7.6 vs 5.4 mo, HR 0.55 ➡️ mOS 17.8 vs 12.9 mo, HR 0.68 ➡️ ORR 51 vs 27% ➡️ G≥3 TRAEs 40 vs 52%; edema 49% Who gets a MET re-biopsy after osimertinib? @LungCancerRx @OncoAlert @oncodaily https://t.co/tJnOIH8yie

This one bothers me. When SAFFRON opened in Aug 2022 there was real equipoise, savo + osi only had single arm data and chemo was the post-osi standard. That changed in June 2025 when SACHI, a randomized phase 3 of the same combo, showed a big PFS benefit over chemo and China approved it. I can see the case for SAFFRON continuing to randomize, SACHI was China only and mostly after 1st or 2nd gen TKIs. I can't see the case for still denying chemo pts the combo once they progressed. Every one of them got in because a biopsy showed MET-driven resistance, and outside China savo was essentially unavailable. That includes pts randomized before June 2025 who progressed after it. SACHI, same combo and same PI, let chemo pts cross over and 43% did. KRYSTAL-12 allowed crossover to adagrasib, and GEOMETRY-E, capmatinib + osi in this same setting, added it by amendment. No SAFFRON amendment adding crossover has been reported, and that likely made the OS gap bigger than it would have been with MET-directed therapy available after chemo.

SAFFRON #ESMO26 shows benefit in PFS/OS for adding MET targeted Rx into osi after 1L-PD. IMO it’s an additional option rather than the new SOC here. Busy space with MET-active (MARIPOSA, CHRYSALIS) and agnostic (COMPEL, TROPION, Opti-TROP) options. Re-biopsy is a limitation.

#ESMO26 🇪🇸 Top Lung Abstracts 🫁 #SAFFRON Phase 3 study of #savolitinib + osimertinib vs. platinum–pemetrexed for MET- driven resistance post osimertinib (N=338) 🎯 MET IHC 3+/ Amp (FISH)>10 🎯 PFS: 7.6 vs 5.4 mo (HR 0.55) 🎯 OS: 17.8 vs 12.9 mo (HR 0.68) 🎯 ORR: 51% vs 27% ⚠️ AEs: Edema & GI toxicity 👉🏽 Clinical Challenge - Although MET resistance post osi can occur 20-30%, it is hard to test for this prospectively in clinic- requires repeat biopsy🔪 #LCSM #LungCancer @EGFRResisters

🚨 Important EGFR-mutated NSCLC results at #ESMO26! Phase III SAFFRON (N=338): Osimertinib + savolitinib vs platinum–pemetrexed after osimertinib progression, with high MET overexpression and/or amplification. OS: 17.8 vs 12.9 mo HR 0.68 (95% CI 0.50–0.91) https://t.co/KF8sZMbyxb

Day 3 (Presidential II) #ESMO26 highlights: 1. Krascendo-1: Divarasib in KRAS G12C NSCLC 2. SAFFRON: Osi + Savolitinib in EGFRm/MET+ NSCLC 3. CLARITY-Gastric01: Sone-Ve CLDN18.2 ADC in Gastric 4. HARMONi-GI1: Ivo + Chemo in 1L BTC 1/5 #OncTwitter #lcsm #gism @myESMO https://t.co/HCh0uT89j7

SAFFRON: osimertinib + savolitinib vs platinum–pemetrexed in EGFR-mutated advanced NSCLC with MET overexpression (IHC 3+ ≥90%) and/or amplification (FISH ≥10 copies) after progression on osimertinib (n=338). Primary endpoint (PFS by BICR): 7.6 vs 5.4 mo, HR 0.55 (95% CI 0.42–0.72). OS: 17.8 vs 12.9 mo, HR 0.68 (95% CI 0.50–0.91), significant at final analysis. Grade ≥3 treatment-related AEs: 40% vs 52% #ESMO26 #LCSM #OncTwitter @BalazsHalmosMD @ADesaiMD @OncoAlert @DrSanjayPopat

🚨 #ESMO26 | SAFFRON Phase III | NEJM Osimertinib + savolitinib vs chemotherapy in MET-positive EGFRm NSCLC after osimertinib: ✅ PFS: 7.6 vs 5.4 mo (HR 0.55) ✅ OS: 17.8 vs 12.9 mo (HR 0.68) ✅ ORR: 51% vs 27% 🎯 A potential new standard of care! #LungCancer #NSCLC https://t.co/5fE6rh1wV2

🫁#ESMO26 I Osimertinib más savolitinib mejora la supervivencia en cáncer de pulmón con alteraciones de MET. 🔎El ensayo fase III SAFFRON, de AstraZeneca, muestra que la combinación mejora la supervivencia global frente a la quimioterapia. @myesmo https://t.co/ky7kkmaxWH

@BalazsHalmosMD Dr Lu showed that adding Savolitinib to Osimertinib is like adding saffron to rice to get a nice paella. 🥘

🚨🫁 ESMO26 | SAFFRON – Fase III Osimertinibe + savolitinibe vs. platina + pemetrexede após progressão ao osimertinibe em CPNPC EGFRm com alterações de MET. ✅ Sobrevida global: 17,8 vs. 12,9 meses (HR 0,68) ✅ 32% de redução no risco de morte ✅ PFS: 7,6 vs. 5,4 meses (HR 0,55) ✅ Resposta objetiva: 51% vs. 27% 🎯 Potencial novo padrão de tratamento, reforçando a importância de investigar mecanismos moleculares de resistência. @OncoAlert @GBOTAlert #ESMO26 #SAFFRON #EGFR #MET #LungCancer #ESMO26 #SAFFRON #Osimertinib #Savolitinib #EGFR #MET #LungCancero

SAFFRON Ph3 met its primary endpoint with osimertinib + savolitinib vs chemo in EGFRm MET overexpressed /amp post osimertinib in NSCLC 🫁 1746 patients screened, 338 randomised. ✅ mPFS 7.6 vs 5.4m HR 0.55 ✅ mOS 17.8 vs 12.9m HR 0.68 ✅ ORR 51% vs 27% ❌ Crossover not permitted Peripheral oedema most common AE. Remember Insight2 with Tepotinib ORR 50%, mPFS 5.6m, mOS 17.8m but Ph2. Congrats to Shun Lu and co-investigators 👏🏼👏🏼👏🏼 #PresidentialDay2 #ESMO26 @myESMO @OncoAlert

Brilliant discussion of the SAFFRON trial by prof Leighl at #ESMO26! As always, incredibly engaging, insightful and clinically focused! Robust, clinically meaningful PFS and OS benefits with osimertinib + savolitinib. Toxicity matters: edema, diarrhea and paronychia require careful management. Key question: Is MET overexpression by IHC enough? IHC identifies eligible patients, but adding FISH can help avoid missing patients with MET amplification. Precision oncology is not just about having the right drug, but also identifying the right patients! We have a clear new SOC here #ESMOAmbassadors #ESMO26 #LungCancer #EGFR #MET

🚨 Awaited SAFFRON #ESMO26 OSI + savolitinib vs ChT EGFRm/MET+ NSCLC after 1L OSI. First positive targeted strategy post-progression!👏👏 🔹 PFS: 7.6 vs 5.4 mo (HR 0.55) 🔹 OS: 17.8 vs 12.9 mo (HR 0.68) @NEJM New roads, challenges: biomarker testing IHC/NGS Tx, Liquid in focus! https://t.co/vfW8thruns

Excellent discussion from Natasha Leighl contextualising Saffron study. MET amplification defined by previous Savannah study. Is IHC enough - yes!Control arm performs as expected, but note that MET is a poor prognostic marker But less than a third have MET 3+. #ESMO26 #LCSM https://t.co/NuBYbao35t

📣 Second Presidential Symposium #ESMO26 👉🏽 SAFFRON: Osimertinib + Savolitinib vs Platinum-Pemetrexed #EGFR #MET # NSCLC 📌 PFS 7.6 vs 5.4m HR 0.55 �� OS 17.8 vs 12.9m HR 0.68 ☣️ 64% grade 3 or higher, OST frequent GI and hematologic @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @NEJM @brunolarvol 👇🏽👇🏽

Another positive Ph.III in NSCLC! #DrShunLu presents SAFFRON: osimertinib + savolitinib vs platinum/pemetrexed after osimertinib in EGFRm/MET+ disease. PFS 7.6 vs 5.4 mo (HR 0.55; p<0.001). OS 17.8 vs 12.9 mo (HR 0.68; p=0.010). #ESMO26 #LungCancer @myESMO @OncoAlert https://t.co/I80Mmftreu

SAFFRON TRIAL: OSIMERTINIB+ SAVOLITINIB COM PAARING WITH PLATINUM PEMETREXED Very proud to participate in this trial @oncoalert @myesmo #ESMO2026 MADRID @Hospital_FJD @quironsalud #LCSM https://t.co/US1Ml4M7XQ

#ESMO26 SAFFRON: osimertinib + savolitinib improves PFS (HR 0.55) and OS (17.8 vs 12.9 months; HR 0.68) after osimertinib in MET-selected EGFRm NSCLC. An all-oral option—but how do we choose versus amivantamab + chemotherapy? No head-to-head data. Biology matters. @myESMO #ESMO26 @Larvol @OncoAlert

🚨 Another important Phase III trial at #ESMO26! #SAFFRON: Osimertinib + savolitinib vs chemotherapy in EGFR-mutant, MET-high NSCLC after osimertinib. 📊 PFS: 7.6 vs 5.4 months 📊 OS: 17.8 vs 12.9 months Both PFS and OS significantly improved! A promising new targeted treatment option, highlighting the importance of biomarker testing after progression. #LungCancer @OncoAlert @StephenVLiu @GlopesMd @ManuelDomine @weoncologists @OpenMedKate

🔥 SAFFRON: osimertinib + savolitinib vs plat-pem in #EGFRm #NSCLC with MET-OE/AMP after osimertinib (n=338), in @NEJM ➡️ mPFS 7.6 vs 5.4 mo | HR 0.55
➡️ mOS 17.8 vs 12.9 mo | HR 0.68
➡️ mDoR 9.7 vs 5.7 mo 🎯 An all-oral targeted option for post-osi MET-driven resistance, with an OS benefit (around 35%) Personal note: one of the first trials I joined after finishing residency. I still remember our patients behind some of these Kaplan-Meier curves @EGFRResisters 🙏 @KolPulseAI @OncoAlert @_SEOM @myESMO @brunolarvol #LCSM #ESMO26

SAFFRON: #ESMO26 MET amp (FISH) or over expression(3+IHC); n338 (screened 1746-19%); 1/3brain mets; PFS HR 0.55; OS HR 0.68 5m longer: mDOR 9.7m ORR 88%; wonder what activity of M2 Is in this group? https://t.co/6e384IkiyK

🆙#ESMO26 Presidential Symposium II: #LCSM 🔥SAFFRON: Osimertinib (Osi) + Savolitinib (Savo) vs Platinum–Pemetrexed (Plat–Pem) in EGFRm MET-Overexpressed (OE) and/or -Amplified (AMP) Advanced NSCLC Post-Osi: Phase (Ph) 3 Primary Results 🎙️Dr. Shun Lu 🔢LBA6 🎯Post-Progression Re-biopsy Mandated 🎯35% of Patients Evaluable for MET testing had MET overexpression (IHC3+ ≥90%) and/or MET amplification (FISH 10+) 🎯Significantly Improved BICR-PFS (7.6 vs 5.4mo, HR 0.55; n=338) and OS (17.8 vs 12.9mo, HR 0.68, p=0.010) 🎯Grade≥3 TEAEs 64% vs 63%; Discontinuation 14% vs 8% ☑️NCT05261399 🔗 https://t.co/bIUj6lFjno @OncoAlert @Larvol @myESMO @IASLC @EGFRResisters

🚨 ?another practice-changing #ESMO2026 result! Phase III #SAFFRON establishes osi + savo as a NEW SOC for EGFRm/MET+ #NSCLC progressing on osimertinib. 📈 PFS: 7.6 vs 5.4m (HR 0.55) 📈 significant OS: 17.8 vs 12.9m (HR 0.68) 🔬 Importance of RE-BIOPSY at progression https://t.co/AOfBjs0XJo

🔥🚨@OncoAlert Hot off the press. Just published @NEJM in conjunction with presentation @myESMO #ESMO26 results of: ⭐️#SAFFRON phase 3 trial of: ❇️#Osimertinib + #Savolitinib (#MET #TKI)! Vs #Chemotherapy (platinum/pemetrexed) 🎯For #2ndLine Tx of #EGFR+ advanced non-small-cell #LungCancer (#NSCLC) with: 🔹#MET #Overexpression or #Amplification or both 🔹#Progression on #Osimertinib Study showed: ‼️Statistically significant & clinically meaningful ⬆️#ProgressionFreeSurvival (primary endpoint) & #OverallSurvival Benefits. ✅#mPFS: 7.6 vs 5.4 months (HR 0.55) ✅#mOS: 17.8 vs 12.9 months (HR 0.68) ✅ ⚠️ Grade ≥3 AEs: 64% vs 63% 👇🏻 https://t.co/f1xNsvRjhC

SAFFRON provides further evidence for 2 key concepts: 1. Continue osimertinib post-progression. 2. Target MET overexpression. My main concern with this particular approach is patient selection. How many patients have c-MET IHC 3+ >90%? @EGFRResisters @myESMO #ESMO26 https://t.co/YCJKZAZcuD

🚨 #ESMO26 Presidential 2 | SAFFRON Ph3 Osimertinib + savolitinib vs platinum–pemetrexed in EGFRm MET-OE and/or -AMP advanced #NSCLC post-osimertinib ✅ mPFS: 7.6 vs 5.4 mo ✅ mOS:17.8 vs 12.9 mo ✅ Median DoR: 9.7 vs 5.7 mo ⚠️Grade ≥3 TRAEs:40% vs 52% #LCSM #EGFR #OncTwitter https://t.co/IXuIsMA3BC

#ESMO26 | SAFFRON | Presidential Session-2 In EGFR-mutant, MET-overexpressed/amplified advanced NSCLC after osimertinib: Osimertinib + savolitinib vs platinum-pemetrexed: 🔹 PFS: 7.6 vs 5.4 mo (HR 0.55) 🔹 OS: 17.8 vs 12.9 mo(HR 0.68) https://t.co/hjW4Zj95YT

ESMO 2026 Presidential 2 | SAFFRON Phase III: Osimertinib + savolitinib vs platinum–pemetrexed in MET-overexpressed/amplified NSCLC progressing on osimertinib (n=338). 📊 Key results: ✅ mPFS: 7.6 vs 5.4 months (HR 0.55; p<0.001) ✅ mOS: 17.8 vs 12.9 months (HR 0.68; p=0.010) ✅ Median DoR: 9.7 vs 5.7 months ⚠️ Grade ≥3 treatment-related AEs: 40% vs 52% ⚠️ Treatment discontinuation due to AEs: 14% vs 8% (all-causality) 🔥 45% reduction in risk of progression and 32% reduction in risk of death! A significant OS benefit with an all-oral, chemotherapy-free combination. Is osimertinib + savolitinib the new standard for MET-driven resistance after osimertinib? @OncoAlert @myESMO #ESMO26 #LungCancer #EGFR #NSCLC

🚨 #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

NATALEE reflections from #ESMO26: what evidence do we need to individualise treatment further? Chemotherapy subgroup findings are exploratory, not proof it can be omitted. @myESMO #bcsm https://t.co/MKkSpTpi3Z https://t.co/s6Hh7SksLF

Day 3 #ESMO26: @jhaveri_komal on refining adjuvant ET in ER+ EBC
✅ CDK4/6i: durable iDFS; OS benefit w/ abema, trend w/ ribo
🆕 lidERA: 1st positive adjuvant oral SERD (HR 0.70)
🧬 ctDNA/MRD: next frontier
🎯 Right drug, right time, right patient
#BCSM #SLUHN 
📋 If giredestrant is approved and CDK4/6i isn't an option (access, toxicity, preference), she'd strongly consider it. Stage I higher-risk: select cases. Stage II–III: CDK4/6i first, SERD after? Sequential trials read out from 2027. #OralSERD #BCSM 
🏎️ ctDNA is like F1 telemetry: a real, early signal. In monarchE, 4-yr iDFS was 87.5% with persistently negative ctDNA, and 93% of patients whose ctDNA turned positive had an event. Does an early "pit stop" help? AFT-70 NAVIGATE is testing that. #ESMO26 #SLUHN 
👩 In patients ≤40, CDK4/6i benefit held: iDFS HR 0.60 (monarchE) and 0.55 (NATALEE). No biomarker yet identifies who won't benefit. #BCSM #EndocrineTherapy @OncologyNetwork @JIPOEditors @myESMO @oncodaily

Encouraging long-term results from NATALEE! 👏 The growing iDFS benefit and emerging OS signal are promising for patients with HR+/HER2− early breast cancer. Great insights from Dr. Gil Morgan and a fantastic way to share the latest updates through the #OAOnTheGo series! 👏 #ESMO26

📌 #OAOnTheGO Series 🎥 in| #ESMO26 Madrid Dr. Gil Morgan (@OncoAlert) breaks down the 6-year NATALEE update! In this episode of #OAOnTheGO, Dr. Gil Morgan, OncoAlert representative, breaks down the 6-year NATALEE update, simultaneously published in Annals of Oncology. https://t.co/6CIPqLaQry

Honored to be part of this discussion with OncoDaily and esteemed colleagues on the 6-year NATALEE data and its implications for breast cancer care. #ESMO26 #BreastCancer @OncoAlert #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/1a44Y2BqdD

🤩 @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

NATALEE 6-year follow up is the best example of the mess that results in the Frequentist framework both in terms of multiplicity, and testing for any effect, even trivial 🧵 https://t.co/0Y587qAU0D

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

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

DASL-HiCap trial #ESMO26 @myESMO @Silke_Gillessen @ANZUPtrials @APCCC_Lugano @oncodaily @OncoAlert 🔴ADT+Darolutamide+prostate/pelvis RT ⬆️ MFS-CI 🟠≠ definition "very high risk" & PSMA/PET not included 🟢Improved MFS-CI, PSA-PFS, CRPC, subsquent tx. But final analysis & OS awaited! 🔵3 studies: STAMPEDE, ENZARAD & DASL-HiCap. ≠ populations, ≠RT to pelvis, N1 benefit across trials. 🟣Good outcomes, need biomarkers

Positive DASL-HiCaP results presented at #ESMO26 @niazi_Dr7 👍Adding #darolutamide to ADT + RT in very-high-risk #ProstateCancer improved ✅4-year MFS (95% vs 88%; HR 0.42), ✅delayed CRPC (HR 0.22) ✅increased time to subsequent hormonal therapy (HR 0.36) All clinically meaningful benefits, while OS remains immature. #ProstateCancer #Radiationtherapy #UrologicOncology @oncodaily @OncoDailyGU @urotoday @ChrisSweens1

Good to have an alternative to adjuvant abiraterone for very high-risk localized prostate cancer. DASL also included early salvage RT after prostatectomy, which matters. OS is still immature, but the early MFS data look impressive. Comorbidities and drug interactions will still drive the choice. #ESMO2026 #prostatecancer

Presidential symposium 1️⃣!! DASL-HCaP: Darolutamide significantly improved MFS-CI when added to ADT and loco-regional RT for very high-risk localised, or biochemically persistent/recurrent prostate cancer. #ESMO26 @myESMO https://t.co/OTtR4z7yv1

🔹 DASL-HiCaP (RT + ADT + darolutamide): MFS HR 0.42, 4-yr MFS 95% vs 88% 
🔹 PROTEUS (surgery + ADT + apalutamide): MFS HR 0.80, 5-yr MFS 78.2% vs 73.5%

🚨📣📣 #ESMO26 presidential: 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

#ESMO26 @niazi_Dr7 DASL-HiCaP (ANZUP1801) n=1,106 | mFU 3.8 yrs | 85% definitive RT darolutamide + ADT + RT v placebo + ADT + RT MFS-CI ➡️ HR 0.42 (0.27–0.66) 4-yr MFS 95% vs 88% https://t.co/oEPnTAMLZc

#ESMO26 #DASLHiCaP #ProstateCancer #pcsm Thread 👇 https://t.co/0VmaUkiykW

DASL-HiCaP: primary MFS endpoint met. In trial-defined very high-risk nonmetastatic prostate cancer, adding darolutamide to ADT + RT improved conventional-imaging MFS: 4-year MFS: 95% vs 88% HR 0.42; P=0.0001 OS not significant yet. #DASLHiCaP #ESMO2026 #ProstateCancer

🚨⭐ #ESMO26 | GU ONCOLOGY — DAY 2 HIGHLIGHTS @urologysummit A major day for both #BladderCancer and #ProstateCancer — with one message coming through clearly: intensification only matters when it delivers durable, clinically meaningful benefit. 🟠 VOLGA | LBA2 — MIBC Perioperative durvalumab + neoadjuvant EV in cisplatin-ineligible/refusing MIBC: ✅ 2-year EFS: 64% vs 45% | HR 0.51 ✅ 2-year OS: 78% vs 69% | HR 0.58 Important survival signal — but not a head-to-head comparison with EV + pembrolizumab. 🔵 DASL-HiCaP | LBA4 Darolutamide + ADT + RT in very-high-risk prostate cancer: ✅ 4-year MFS: 95% vs 88% | HR 0.42 OS remains immature; still investigational. 🔵 PEACE-1 | 2215O After 7.7 years of follow-up in de novo mCSPC: ✅ Median OS: 6.2 vs 4.4 years ✅ 8-year OS: 40.3% vs 27.1% This is what durable treatment intensification looks like. 🔵 PROTEUS substudy | LBA53 Perioperative apalutamide + ADT around prostatectomy: ✅ EFS HR 0.38 Promising — but longer follow-up and setting-specific interpretation are essential. 🧬 STAMPEDE / Decipher | 2045O Genomic risk may help identify who derives greater benefit from abiraterone for distant-metastasis prevention. Interesting biomarker signal — not yet a basis for de-escalation. 🟠 NIAGARA molecular analysis | 4741RO Exploratory EFS signals across molecular subtypes, including basal-squamous disease. Still no validated biomarker to withhold perioperative durvalumab. 🟠 EV-103 | 4740RO Long-term EV + pembrolizumab follow-up: ✅ Estimated 5-year OS: 33% Durability matters — and so does late toxicity. 🟠 GDFATHER-NEO | 4757RO Visugromab + nivolumab: ✅ pCR: 33.3% vs 7.7% Intriguing, but exploratory in a small dataset. ⭐ MY CLINICAL PEARL Not every form of intensification is equal. What matters is proven survival or metastasis prevention, weighed against toxicity, patient selection, quality of life, and long-term treatment burden. Precision + durable benefit — not just higher response rates. @gbanna74 @ravikanesvaran @neerajaiims @PGrivasMDPhD @Sebastiano_Buti @dmukherji @alison_tree @DrYukselUrun @yekeduz_emre @AgrawalTrush #GUOncology #MIBC #mCSPC #PrecisionOncology #OncoAlert

Results from the DASL-HiCaP study were presented on October 24, 2026. DASL-HiCaP (ANZUP1801) – ESMO 2026 Study objective: To evaluate the addition of darolutamide to standard androgen deprivation therapy (ADT) and radiotherapy in patients with very high-risk localized prostate cancer. Phase III: 1,106 patients; randomized, double-blind, placebo-controlled. Treatment: Darolutamide 600 mg twice daily for 96 weeks + ADT and radiotherapy. Control: Placebo + ADT and radiotherapy. Median follow-up: 3.8 years. Primary endpoint: Imaging-based metastasis-free survival (MFS-CI) was significantly improved: HR 0.42 (95% CI 0.27–0.66; p=0.0001). The risk of PSA progression or death was reduced by 53%: HR 0.47 (95% CI 0.33–0.67). Overall survival: The difference was not yet statistically significant: HR 0.88 (95% CI 0.49–1.59). Safety Grade ≥3 adverse events occurred in 43% of patients in the darolutamide group and 36% in the placebo group. Grade ≥2 fatigue/asthenia was reported in 14% and 10% of patients, respectively. Clinical Take-Home Message Darolutamide + ADT + radiotherapy increased 4-year metastasis-free survival from 88% to 95% in patients with very high-risk localized prostate cancer. This represents an absolute improvement of 7 percentage points and a 58% relative reduction in the hazard of metastasis or death. These findings support treatment intensification in this patient population. However, as overall survival data remain immature, an overall survival benefit should not yet be considered established. Link : https://t.co/YmlFyx06Au #DASLHiCaP #ESMO2026 #ProstateCancer #Darolutamide #UroOncology

DASL-HiCaP: Darolutamide plus RTE in very high risk localized prostate cancer increases MFS (HR 0.42) and other secondary objectives. mFU: 2 years. A new SoC?: NGI and Biomarkers are necessary for patients selection. #ESMO26 #ProstateCancer @myESMO @sogug1 @_SEOM https://t.co/AIyPfPLhhJ

1/n Major congrats to our DASL team, especially to @ChrisSweens1 and @niazi_Dr7, and a big thanks to the patients. Working with @ANZUPtrials and @ThePCCTC on DASL as US lead has been a career highlight. I'd contend this establishes a new standard of care in DASL very-high risk PCa. The conventional-image defined MFS benefit with the addition of Darolutamide to RT+ADT was extraordinarily robust; the DSMC recommended reporting out at IA. #ESMO26, #radonc, #medtwitter. @MSKCancerCenter @MSK_RadOnc. #pcsm Brief 🧵

DASL-HiCaP: darolutamide on top of 96 weeks of ADT plus RT improved MFS in very high-risk localized prostate cancer, HR 0.42, 4-yr MFS 95% vs 88%. 📈 n=1,106, interim at 67% of events, 46 mo follow-up. OS immature 📝 Thanks to @Silke_Gillessen putting this into context STAMPEDE M0 (HR 0.53) and ENZARAD (HR 0.88): not contradictory, the ARPI benefit tracks metastatic risk 🎯 N1 is the clearest indication. N0 is less clear, and Gleason seems to matter Every patient got pelvic RT, so who needs it in N0 not yet answered. @Niazi_Dr7 #ProstateCancer #GUonc #ESMO26

Rather a brilliant discussion at the presidential #ESMO26 for the DASL very high risk prostate cancer trial The future is patient selection. The clearest indication is in pateints with N1 disease supported by results from thr other trials @OncoAlert @ChrisSweens1 @Uromigos https://t.co/Sr5myx9C6j

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

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.

🚨📣📣 #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

📊 HARMONi-GI1 - Phase 3 (Akeso release, ESMO LBA8) 🎯 First-line advanced biliary tract cancer, China 💊 Ivonescimab (PD-1/VEGF) + gem-cis vs durvalumab + gem-cis 👥 682 patients, interim analysis ✅ OS 14.9 vs 12.1 mo, HR 0.75 ✅ PFS 8.4 vs 5.8 mo, HR 0.61 📈 ORR 53.8% vs 32.5% 🩸 Grade ≥3 bleeding 1.5% vs 1.8% ⚠️ China only, interim analysis A head-to-head win over TOPAZ-1. The US ECOG-ACRIN trial will decide it for Western patients. Potential new SOC? Yes, but: ⚠️ This is an interim analysis with immature follow-up. Median follow-up was 14.3 months, and the 18-month OS difference rests on few patients still at risk. TOPAZ-1's benefit grew with longer follow-up (HR 0.80 → 0.76 → 0.74 → 0.75). Durability needs to be confirmed in both directions. ⚠️ Post-progression treatment was imbalanced. Only 31.8% of the ivonescimab arm received further therapy vs 45.9% of controls. This would normally dilute an OS benefit, so the HR may be conservative. However, the reasons for the gap (clinical decline, toxicity, how the denominator was defined) need to be in the full report. ⚠️ Subsequent therapy differs from US practice. In the US, second-line care for BTC increasingly involves targeted agents for FGFR2, IDH1, HER2, and others. Whether a China-only OS result carries over depends partly on that downstream care. FDA has stressed that subsequent therapies must match US practice when OS is the endpoint #BTC #Cholangiocarcinoma https://t.co/vnJvi5WVcR

🟢 #ESMO26 HARMONi-GI1 (ph III): ivonescimab + gem/cis beat durvalumab + gem/cis in 1L advanced biliary tract cancer. OS 14.9 vs 12.1 mo (HR 0.75) 18-mo OS 44.0% vs 32.5% Active comparator! Caveats: China-only study, added toxicity. #gicsm https://t.co/2F5d9TuCTF

📍HARMONi-GI1🍁 #biliarytractcancer #esmo2026 #presidentialSymposium2 - phase 3 study , ivonescimab, a PD-1/VEGF bispecific antibody, plus cis/gem versus durvalumab plus cis/gem as first-line treatment for advanced BTC 📍Results - Median OS was significantly improved with ivonescimab plus chemo vs durvalumab plus chemo (14.9 vs. 12.1 months; HR 0.75, P = 0.0031). - Median PFS was 8.4 vs. 5.8 months (HR 0.61, P <0.0001). - The ORR was 53.8 % vs. 32.5 % (P <0.0001). @myESMO @OncoDailyGI @oncodaily

#ESMO26: Akeso detailed its Phase 3 biliary cancer win for ivonescimab, with survival data drawing comparisons to Keytruda. https://t.co/ur2S0LgyNP

James Harding disccuses harmoniGI 1 study #ESMO2026 https://t.co/ZwOYFMMUWR

🚨 ESMO 2026 | HARMONi-GI1 Phase III, 1L advanced biliary tract cancer: ivonescimab (PD-1 × VEGF) + GemCis vs durvalumab + GemCis (n=682) 📊 OS: 14.9 vs 12.1 m (HR 0.75; p=0.0031) 📊 PFS: 8.4 vs 5.8 m (HR 0.61) 📊 ORR: 53.8% vs 32.5% The bispecific era is gathering pace. 🧬

Day 3 (Presidential II) #ESMO26 highlights: 1. Krascendo-1: Divarasib in KRAS G12C NSCLC 2. SAFFRON: Osi + Savolitinib in EGFRm/MET+ NSCLC 3. CLARITY-Gastric01: Sone-Ve CLDN18.2 ADC in Gastric 4. HARMONi-GI1: Ivo + Chemo in 1L BTC 1/5 #OncTwitter #lcsm #gism @myESMO https://t.co/HCh0uT89j7

🔬Ivonescimab now represent a promising emerging therapeutic option - exciting progress for cholangiocarcinoma and biliary tract cancer patients @curecc https://t.co/H750CgmfiG

HARMONi-GI1: OS 14.9 vs 12.1 months. Grade 3–4 AEs: 82% vs 72%. A meaningful survival gain, with added toxicity. @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 https://t.co/17ZBsufXOl

Interim analysis of HARMONi-GI1 phase III findings of #Ivonescimab (bispecific Ab for PD-1/VEGF) + chemo vs. durvalumab + chemo for treatment-naive #biliarytract #cancer (N=682). 👏👏 🔹Primary endpoint: OS of 14.9M vs. 12.1 (HR = 0.75) 🔹PFS: 8.4 vs. 5.8M; HR = 0.61 🔹ORR = 53.8% vs. 32.5% 🔹Subsequent therapies was 31.8% vs. 45.9% (more so in control arm) @curecc #cancer #cancerresearch @OncoAlert @SMMT_TX

HARMONi-GI1 phase 3 trial of ivonescimab + chemo in 1L advanced #BTC -OS 14.9 vs 12.1 mos HR 0.75 p 0.0031 -PFS 8.4 vs 5.8 mos HR 0.61 p<0.0001 -ORR 53.8 vs 32.5% p<0.0001 A new standard of care in China. Do we need a trial in Western countries? #ESMO26 #ESMOAmbassadors @myESMO https://t.co/b2U1WNUHf6

HARMONI-GI1 at the @myESMO #ESMO26 #Presidential of CisGem + #ivonescimab vs durvalumab in #firstline #BiliaryMalignancies ✅OS HR 0.75, mOS 12.1vs14.9 ✅PFS HR 0.61, mPFS 6.8vs8.4 ✅ORR 53.8vs32.5 🌐China only BUT 😊This is a positive trial 🥳VEGF is back #ESMOAmbassadors https://t.co/lK6iJSkPlN

HARMONI-Gi comparing Ivonescimib plus chemo vs Durvalumab plus chemo in 1L advance BTC, Ivonescimib significantly improves PFS and OS over Durvalumab. #ESMO2026 @myESMO @curijoey @OncoAlert https://t.co/lh2yTJgD30

🚨 #ESMO26 Plenary | HARMONi-GI1 Ivonescimab + chemo improves outcomes vs durvalumab + chemo in 1L advanced BTC 🇨🇳 - OS: 14.9 vs 12.1 mo (HR 0.75)
- PFS: 8.4 vs 5.8 mo (HR 0.61)
- ORR: 53.8% vs 32.5% @OncoAlert #GIOncology @myESMO https://t.co/YbaDUktknQ

🔥HARMONi-GI1 ph3 advanced #BTC ➡️ivonescimab/GC v durva/GC mFU 14.3mths; China only & interim ✅ iCCA 58% ORR 53.8v32.5%; mPFS 8.4 v 5.8mths ✅mOS 14.9 v12.1mths HR0.75 ➡️AE rate high in both Control arm OS represents❗️VEGF in BTC ⭐️ looks promising @myESMO #ESMO26 @OncoAlert https://t.co/8HVkjxvaFq

📣 Second Presidential Symposium #ESMO26 👉🏽 Ivonescimab plus chemotherapy versus durvalumab plus chemotherapy as first-line treatment for advanced biliary tract cancer: A randomized, controlled, double-blinded, phase 3 trial (HARMONi-GI1) 🗣️ Dr. Zhou 📌 PFS 8.4 vs 5.8m HR 0.61 📌 OS 14.9 vs 12.1m HR 0.75 ☣️ Most frequent hematologic, AST elevation, proteinuria ☣️ Grade 3 or higher 82 vs 72% @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @NEJM @brunolarvol 👇🏽👇🏽

#ESMO26 🚀 HARMONi-GI1 | Phase III 🇨🇳 682 pts | 1L advanced BTC 💊 Ivonescimab+GemCis vs Durva+GemCis 🏆 OS: 14.9 vs 12.1 mo (HR 0.75) 📈 PFS: 8.4 vs 5.8 mo (HR 0.61) 🎯 ORR: 53.8% vs 32.5% ⚠️ G3–4 AEs: 82% vs 72.3% 💡 Potential new 1L SoC @OncoAlert https://t.co/Xcnb18yFqT

🆙#ESMO26 Presidential Symposium II 🔥HARMONi-GI1: Ivonescimab Plus Chemotherapy Versus Durvalumab Plus Chemotherapy as First-Line Treatment for Advanced Biliary Tract Cancer: A Randomized, Controlled, Double-Blinded, Phase 3 Trial 🎙️Dr. Jian Zhou 🔢LBA8 🎯Met Primary Endpoint 🎯OS (14.9 vs 12.1mo, HR 0.75, p=0.0031; n=682) 🎯PFS (8.4 vs 5.8mo, HR 0.61) 🎯ORR (53.8% vs 32.5%) 🎯No New Safety Signals ☑️NCT06591520 🔗 https://t.co/bIUj6lFjno @OncoAlert @Larvol @myESMO

💥 Ivonescimab, bi-specific PD-1/VEGF, hits a 4th positive Phase III randomized clinical trial, first outside lung cancer indications already approved in China. ✅ 1 L Biliary-tract carcinoma: Ivo + chemo >> Durva + chemo, better ORR, PFS, and OS #ESMO26 https://t.co/2BrYeqTfpH

🔥Presidential session at ESMO 2026 🔥 HARMONi-GI1 ph-3: Ivonescimab + CTx vs durvalumab + CTx as 1L for BTC #ESMO26 #ESMOAmbassadors 👉ORR: 53.8 vs. 32.5 % 👉mPFS: 8.4 vs 5.8 mo 👉mOS: 14.9 vs. 12.1 mo 🧐 Very promising Chinese data, would be great to see data in a global population @myESMO @ASCO

🚨 #ESMO26 Presidential 2 | HARMONi-GI1 Ph3 Ivonescimab (PD-1/VEGF bispecific) + GemCis vs durvalumab + GemCis as 1L in advanced BTC (n=682; China) ✅ mOS: 14.9 vs 12.1 mo (HR 0.75) ✅ mPFS: 8.4 vs 5.8 mo (HR 0.61) ✅ ORR: 53.8% vs 32.5% ❌new signals #GIOnc #BTC #OncTwitter https://t.co/h31JRRk2V7

4 studies I’m watching today at #ESMO26 Presidential Symposium II (16:30 CET): KRAScendo 1, SAFFRON, CLARITY-Gastric 01 and HARMONi-GI1. Which one are you waiting for? I’ll post notes right after each LBA. #Oncology https://t.co/2qVqWcF773

RCC wrap-up, this morning’s session 🍀 LITESPARK-012: Another triplet that failed in metastatic clear-cell RCC, following COSMIC-313. Adding neither belzutifan nor anti-CTLA-4 to pembrolizumab + lenvatinib showed any benefit. The CPI/anti-VEGF doublet remains the backbone. Stacking yet another existing drug on top doesn't help us better understand the biology of the disease. 🍀 XmAb819 phase 1: Welcoming T-cell engagers to ccRCC. For years we've labeled tumors that don't respond to checkpoint inhibitors as "cold" in daily practice, as if there were only one immunological mechanism. T-cell engagers are challenging that laziness, and not only in immune-excluded tumors. In immunogenic RCC, even in heavily pretreated patients (median 3 prior lines, including CPI), we saw an impressive 27% ORR and 68% DCR. 🍀 Ivonescimab phase 2: After NSCLC and biliary tract cancer, the VEGF/PD-1 bispecific keeps moving forward. In first-line IMDC favorable-risk metastatic RCC, it showed a 57% ORR and 95% DCR, with a side-effect profile quite different from that of TKIs. Patients with advanced cancer are surely the last group in society who care which country a drug comes from. Here's hoping every effective drug becomes globally accessible. #ESMO2026 #kidneycancer #RCC @OncBrothers @OncoAlert @myESMO @DrYukselUrun @dr_yakupergun

🚀Presidential #ESMO26 HARMONi-GI1 in advanced BTC 🟢Ivonescimab-GemCis vs Durva-Gemcis ✅mOS: 14.9 vs. 12.1 months; HR 0.75, 95% CI 0.61-0.92, P = 0.0031 ✅mPFS: 8.4 vs. 5.8 months, HR 0.61, 95% CI 0.51-0.72, P <0.0001 ✅ORR: 53.8 % vs. 32.5 % (P <0.0001) #cancer #oncology #MedX @OncoAlert #biliary #cholangiocarcinoma #gallbladder

#ESMO26 | HARMONi-GI1| Presidential Session-2 In 1L advanced biliary tract cancer, ivonescimab + chemo vs durvalumab + chemo: 🔹 OS: 14.9 vs 12.1 mo 🔹 PFS: 8.4 vs 5.8 mo 🔹 ORR: 53.8% vs 32.5% A clinically meaningful improvement in OS and PFS against an active SoC comparator https://t.co/haLYmXJHBw

ESMO 2026 presidential 2 | HARMONi-GI1: Ivonescimab beats durvalumab in advanced biliary tract cancer! Phase III trial (n=682): Ivonescimab (PD-1/VEGF bispecific antibody) + gemcitabine/cisplatin vs durvalumab + gemcitabine/cisplatin in 1L advanced BTC. 📊 Key results: ✅ Median OS: 14.9 vs 12.1 months (HR 0.75; p=0.0031) ✅ Median PFS: 8.4 vs 5.8 months (HR 0.61; p<0.0001) ✅ ORR: 53.8% vs 32.5% (p<0.0001) ✅ Manageable safety profile; no new safety signals. 🔥 25% reduction in risk of death and 39% reduction in risk of progression! A rare head-to-head phase III victory against an established immunotherapy standard in BTC. Could PD-1/VEGF bispecific antibodies replace conventional PD-L1 inhibition in first-line BTC? @OncoAlert @myESMO #ESMO26 #BiliaryTractCancer #Oncology

PERSEE at #ESMO26: PD-L1 ≥50% advanced NSCLC. Pembrolizumab + chemo vs pembrolizumab alone: PFS: 16.1 vs 6.9 mo (HR 0.56) OS: 50.2 vs 29.9 mo (HR 0.77; not statistically significant) Grade ≥3 TRAEs: 54% vs 19% Better disease control, more toxicity. Individualize. #LungCancer

My *practice changing* take home messages from #ESMO26 to NHS lung cancer teams: Immediate change: 1. PERSEE. Bottom line - Chemo still alive for PDL1 >50%. Median OS 50.2m Vs 29.9m. Works just as well for 90-100% group too Fitter, younger should get Chemo even PDL1 100% #ESMO26

Congrats to the GFPC team on PERSEE at #ESMO26 👏 PD-L1 ≥50% NSCLC: pembro + chemo vs pembro alone
• mPFS 16.1 vs 6.9 mo (HR 0.56)
• ORR 78% vs 50%
• OS trend (HR 0.77, NS)
• G≥3 TRAEs 54% vs 19% Randomised evidence for an everyday question in Europe. #ESMOAmbassadors

Important #ESMO26 study, published in @Annals_Oncology ! In the phase 3 PERSEE trial adding chemotherapy to pembrolizumab in advanced lung cancer with PD-L1 ≥50% improved median progression-free survival from 6.9 to 16.1 months (HR 0.56). Median overall survival was 50.2 vs 29.9 months (HR 0.77), although the difference was not statistically significant. Grade ≥3 treatment-related adverse events increased (54% vs 19%). An important finding for first-line treatment decisions in PD-L1-high lung cancer.

Another practice changing result for lung oncology at #ESMO26: PERSEE trial 👉 Academic 🇫🇷 multicentre study 👉 Which is best in 1L PD-L1 >50% NSCLC: pembro (P) or chemo+pembro (CT-P)? What do we know already? 🔹Retrospective study suggested modest benefit of CT-P What did this study do? 🔸 Phase 3, multi-centre, randomised 🔸 Local PD-L1 testing 🔸 1:1 P or CT-P 🔸 1’ end-point = PFS What was found? CT-P… ✅ Improved mPFS in whole popn (HR 0.56) ✅ Improvement was in all PD-L1 levels (50-74; 75-90; 90-100%) ✅ Improvement in mOS (HR 0.77), not powered for significance ✅ Increased ORR: 77% v 50% ✅ Reduced early progression Thoughts: 🤔 An easy way to improve the outcome for most of your PD-L1 >50% pts: add chemo to the pembro 🤔 CT-P still not for everyone: less/no benefit in >70yrs, and squamous histology 🤔 Shame PS=2 not included, to make this more real-world 🤔 Had not expected CT-P to be better across all PD-L1 levels 🤔 Pembro only still has a role in select PD-L1 high, especially >90% with KRAS G12C Will this change my practice? 👉 I already use CT-P in PD-L1 50-80%, but I will now use it in >80% for most (but not all) pts 👏 Great study. Congratulations to authors #LCSM

🚨 #ESMO26 | Top Lung Abstracts🫁 PERSEE: Phase 3 🇫🇷 study of pembrolizumab alone vs chemo+pembro for PD-L1-high 🔥 PFS: 16.1 vs 6.9 mo (HR 0.56) 🎯 ORR: 77.5% vs 50.3% ⚠️ Early progression: 5.8% vs 26.5% 📊 OS: 50.2 vs 29.9 mo (HR 0.77; NS) 👉🏽 Maybe more is better for select patients 👉🏽Benefit persisted even with PD-L1 ≥90%—but grade ≥3 TRAEs increased (53.8% vs 19.3%). More disease control but more toxicity. #lcsm #immunotherapy

PERSEE | ESMO 2026 — Does PD-L1 ≥50% mean we can skip chemotherapy? A randomized Phase III trial challenges that assumption. Four key questions, four parts: 1/4 | WHY ADD CHEMO? 321 patients randomized to pembrolizumab ± platinum chemotherapy. 2/4 | DOES IT WORK? PFS: 16.1 vs 6.9 months (HR 0.56). ORR: 77.5% vs 50.3%. OS: 50.2 vs 29.9 months (HR 0.77; not statistically significant). 3/4 | WHAT IF PD-L1 ≥90%? PFS: 25.4 vs 7.1 months (HR 0.60). Even very high PD-L1 does not eliminate the signal for chemotherapy benefit. 4/4 | WHAT'S THE PRICE? Grade ≥3 treatment-related AEs: 54% vs 19%. Greater disease control, substantially greater toxicity. Take-home: PERSEE strengthens the case for chemoimmunotherapy when rapid disease control matters. But without proven OS superiority, pembrolizumab alone remains a valid option. Better PFS ≠ chemotherapy for everyone. Descourt R et al. Ann Oncol. 2026. https://t.co/1R7mKrCQcY @myESMO @OncoAlert #ESMO26 #NSCLC #MVOnco

PERSEE trial addresses a question I often discuss with patients: if PD-L1 is >50%, should we use pembrolizumab alone or add chemotherapy? In this randomized phase III trial, adding chemotherapy improved median PFS from 6.9 to 16.1 months (HR 0.56) and response rates from 50.3% to 77.5%. That is a substantial difference in disease control. The tradeoff was also substantial: grade ≥3 treatment-related toxicity increased from 19.3% to 53.8%. Median OS is numerically way longer, 50.2 vs 29.9 months, but the difference was not statistically significant (HR 0.77; 95% CI 0.57–1.05). We should be careful about how we describe that finding. These results would strengthen my preference for chemoimmunotherapy in a fit patient with symptomatic or rapidly progressing disease, where an early response matters. I would still discuss pembrolizumab alone with selected patients. High PD-L1 expression is useful, but the treatment decision also needs to account for disease burden, symptoms, comorbidities and what the patient values. I’d particularly like to see the quality of life results, subsequent treatments and detailed subgroup analyses. This is a very important and relevant study that gives us better evidence for a very practical conversation. Decroisette et al. PERSEE, ESMO 2026, abstract 2614O. @LungSummit @lcrf_org @myESMO @UVMLarnerMed @UVMcancercenter #ESMO26 #LCSM #NSCLC

PERSEE (2614O): Randomized phase 3, 321 pts w/ untreated advanced NSCLC, PD-L1 ≥50%: pembro + platinum chemo vs pembro alone. mPFS 16.1 vs 6.9 mo (HR 0.56). mOS 50.2 vs 29.9 mo (HR 0.77), not significant. G≥3 TRAEs 54% vs 19%. #ESMO26 #LCSM https://t.co/zT6q08skru https://t.co/XNdfAoTWKE

Pembrolizumab with or without platinum-based chemotherapy as first-line treatment in advanced NSCLC expressing PD-L1 ≥50%: The PERSEE randomized phase III trial (GFPC 01-2020) #cancer #oncology #MedX @OncoAlert https://t.co/tbjU1i7Yzn

🔥🚨@OncoAlert Hot off the press. Just published @Annals_Oncology in conjunction with presentation @myESMO #ESMO26 results of: ⭐️#PERSEE phase 3 trial of: ❇️#Pembrolizumab monotherapy Vs #Pembrolizumab + #Chemotherapy 🎯For #1stLine Tx of advanced non-small-cell #LungCancer (#NSCLC) with HIGH #PDL1 (PD-L1 ≥50%). Study showed: ‼️Statistically significant & clinically meaningful ⬆️#ProgressionFreeSurvival Benefit. ✅#mPFS: 16.1 vs 6.9 mo (HR 0.56) ❓#mOS: 50.2 vs 29.9 mo NOT Statistical Significant (HR 0.77; 95% CI, 0.56–1.05) Study not powered for #OverallSurvival 👇🏻 https://t.co/V3yc1U84Bi

Unclear whether mono arm underperformed and the exact role of PD-L1 in Persee. Median PFS mono ICI in PD-L1 >90 : 10-15 months vs 7 months in Persee in all high PD-L1 subcategories. OS>50 months with chemo-ICI unrealistic..need more follow up https://t.co/MP90Br4qTj

המשך עדוכנים מהכנס: #ESMO2026 #ESMO26 @myESMO מחקר PERSEE ששאל האם כדאי להוסיף כימותרפיה לאימונותרפיה גם כש־PD-L1 ≥50%? המחקר שסיפק השוואה ישירה בין pembrolizumab בלבד לבין השילוב עם כימותרפיה ב־NSCLC מתקדם בחולים עם NSCLC מתקדם וביטוי PD-L1 של 50% ומעלה, ללא שינויים אונקוגניים הניתנים לטיפול ממוקד בהתאם לקריטריוני המחקר, שתי אסטרטגיות טיפול מרכזיות עומדות זו לצד זו: pembrolizumab כמונותרפיה, או pembrolizumab בשילוב כימותרפיה מבוססת פלטינום. עד PERSEE, לא היו נתונים מניסוי Phase III שהשלים השוואה ישירה בין שתי האסטרטגיות באוכלוסייה זו. השאלה הקלינית הייתה מרכזית: האם הוספת כימותרפיה משפרת את השליטה במחלה, ומה המחיר מבחינת רעילות? מה למדנו מהמחקרים הקודמים? 1. KEYNOTE-024 ביסוס המונותרפיה המחקר השווה pembrolizumab לכימותרפיה מבוססת פלטינום בחולים עם PD-L1 ≥50%, והדגים יתרון לטובת pembrolizumab ב־PFS ובהישרדות הכוללת. בכך ביסס את המונותרפיה כאפשרות טיפול מרכזית בקו הראשון. 2. KEYNOTE-189 ו־KEYNOTE-407 ביסוס השילוב מחקרים אלה הראו כי הוספת pembrolizumab לכימותרפיה משפרת תוצאות לעומת כימותרפיה בלבד, הן ב־NSCLC שאינו קשקשי והן במחלה קשקשית. התועלת נצפתה גם בחולים עם PD-L1 ≥50%. עם זאת, מחקרים אלה לא השוו ישירות בין השילוב לבין pembrolizumab בלבד אלא מול כימותרפיה בלבד 3. KEYNOTE-598 שאלה טיפולית אחרת הוספת ipilimumab ל־pembrolizumab לא שיפרה את התוצאות והגבירה את הרעילות. חשוב לזכור שמדובר בהוספת אימונותרפיה מסוג אחר, ולא בהוספת כימותרפיה. לכן אין להסיק ממחקר זה ישירות לגבי התועלת האפשרית של כימותרפיה בשילוב עם pembrolizumab. מה בדק המחקר PERSEE? מדובר במחקר פאזה 3 אקראי, פתוח, שנערך ב־28 מרכזים בצרפת. במחקר השתתפו 321 חולים עם NSCLC מתקדם, שלא קיבלו טיפול סיסטמי קודם למחלה המתקדמת, עם PD-L1 ≥50% ו־ECOG 0–1. החולים הוקצו ל־pembrolizumab בלבד או ל־pembrolizumab בשילוב כימותרפיה מבוססת פלטינום. נקודת הסיום הראשית הייתה PFS, בהערכה מרכזית סמויה להקצאת הטיפול. חציון המעקב היה 38.7 חודשים. התוצאות המרכזיות: PFS נקודת הסיום הראשית חציון PFS היה 16.1 חודשים בשילוב לעומת 6.9 חודשים במונותרפיה של אינותרפיה בלבד HR 0.56 (95% CI 0.43–0.74; P<0.001). כלומר, השילוב הפחית בכ־44% את הסיכון היחסי להתקדמות המחלה או למוות בהשוואה ל־pembrolizumab בלבד. ORR שיעור התגובה האובייקטיבית 77.5% בשילוב לעומת 50.3% במונותרפיה. התקדמות מוקדמת: שיעור ההתקדמות המוקדמת היה 5.8% בשילוב לעומת 26.5% במונותרפיה. מדובר בנקודת סיום חקרנית, שהוגדרה כהתקדמות קלינית ו/או רדיולוגית לפני בדיקת ההדמיה הראשונה או במועד הבדיקה, סביב שישה שבועות. משך התגובה: חציון משך התגובה היה 30.0 חודשים בשילוב לעומת 15.6 חודשים במונותרפיה. עם זאת, ה־HR לאובדן תגובה או מוות היה 0.88 (95% CI 0.60–1.29), ולכן אין לקבוע שההבדל במשך התגובה מובהק סטטיסטית. הישרדות כוללת OS חציון OS היה 50.2 חודשים בשילוב לעומת 29.9 חודשים במונותרפיה. HR 0.77 (95% CI 0.56–1.05). ההבדל המספרי נוטה לטובת השילוב, אך לא הודגם יתרון מובהק סטטיסטית ב־OS. המחקר תוכנן לבחון את ה־PFS ולא היה בעל עוצמה מספקת להוכחת הבדל בהישרדות הכוללת. בטיחות: תופעות לוואי הקשורות לטיפול בדרגה 3 ומעלה התרחשו ב־54% מהחולים שקיבלו את השילוב, לעומת 19% במונותרפיה. שיעור תופעות הלוואי החיסוניות בדרגה 3 ומעלה היה 13% בשתי הקבוצות. המשמעות הקלינית: מחקר PERSEE מוסיף ראיות אקראיות ישירות לשאלה שלא נפתרה במחקרים הקודמים. בחולים עם NSCLC מתקדם ו־PD-L1 גבוה, הוספת כימותרפיה ל־pembrolizumab שיפרה באופן מובהק את ה־PFS והייתה קשורה לשיעור תגובה גבוה יותר ולשיעור נמוך יותר של התקדמות מוקדמת. יתרונות אלה עשויים להיות חשובים במיוחד בחולים שבהם יש צורך בשליטה מוקדמת במחלה. מנגד, יש להביא בחשבון את העלייה המשמעותית ברעילות. חשוב להדגיש כי המחקר לא הוכיח יתרון מובהק סטטיסטית ב־OS, ונתוני איכות החיים לא נכללו בדיווח הנוכחי. כמו כן, תוצאות המחקר אינן קובעות שהשילוב עדיף לכל חולה עם PD-L1 ≥50%. בחירת הטיפול צריכה להיות מותאמת למאפייני המחלה, לעומס הגידולי ולקצב התקדמותה, למצבו התפקודי של המטופל, לתחלואה הנלווית, לסבילות הצפויה לטיפול ולהעדפות המטופל. בשורה התחתונה: המסר המרכזי של PERSEE: הוספת כימותרפיה ל־pembrolizumab משפרת באופן מובהק את השליטה במחלה, אך במחיר של רעילות מוגברת. המחקר מחזק את מקומו של השילוב כאפשרות טיפול בקו הראשון גם בחולים עם PD-L1 גבוה, במיוחד כאשר נדרשת שליטה מוקדמת במחלה והמטופל מסוגל לשאת את הטיפול. עם זאת, הוא אינו מבטל את מקומה של מונותרפיה ב־pembrolizumab. ההחלטה בין שתי האסטרטגיות צריכה להתקבל באופן פרטני, תוך שקילת התועלת הצפויה מול הסיכון.

PD-L1 ≥50% does not make the chemotherapy question disappear. PERSEE directly compared pembrolizumab + platinum-based chemotherapy with pembrolizumab alone in untreated EGFR/ALK-negative advanced NSCLC. • Primary BICR-PFS: 16.1 vs 6.9 months • HR 0.56; P<0.001 • OS: 50.2 vs 29.9 months, but NOT statistically significant: HR 0.77; 95% CI 0.57–1.05 • Grade ≥3 treatment-related AEs: 53.8% vs 19.3% A clear PFS benefit comes with substantially more toxicity. Which PD-L1-high patients can reasonably avoid chemotherapy—and which need the higher response rate and longer disease control? @StephenVLiu @CharuAggarwalMD @myESMO @OncoAlert #PERSEE #ESMO26 #LCSM

🚨 PD-L1 ≥50% in NSCLC: Is pembrolizumab alone enough? 🔥 PERSEE Phase III | #ESMO26 Concomitant publication in Annals of Oncology. Pembrolizumab + chemotherapy vs pembrolizumab alone: 📊 PFS: 16.1 vs 6.9 months (HR 0.56) 🎯 ORR: 77.5% vs 50.3% ⚠️ Grade ≥3 toxicity: 54% vs 19% OS: 50.2 vs 29.9 months (HR 0.77), not statistically significant. 💡 Verdict: Better disease control, but at a substantial toxicity cost. Is PD-L1 ≥50% alone sufficient to omit chemotherapy? @ESMO_open @myesmo @ASCO @oncoalert #ESMO26 #LungCancer

Off the rousing #ESMO26 oral presentation from Dr. @decroisette, the phase III PERSEE trial with simultaneous publication @Annals_Oncology. Combination of chemotherapy + pembrolizumab superior to pembro in PDL1 high NSCLC: PFS 16.1 vs 6.9m, HR 0.56! https://t.co/l2d3Sdd9CH

‼️ In first line treatment of advanced PD-L1 ≥50% NSCLC, PERSEE demonstrates a significant improvement of PFS with pembro-CT compared to pembro monotherapy regardless of PDL1 level of (over)expression. Practise changing trial. @myESMO @OncoAlert #ESMO26 👏👏👏 @decroisette https://t.co/PXSKgrImYX

Impressive results Academic III PERSEE #ESMO26 @Annals_Oncology First positive random trial adding chemo to pembro in PD-L1 ≥50% NSCLC: 🔹 PFS: 16.1 vs 6.9 mo HR 0.56 🔹 OS: 50.2 vs 29.9 mo HR 0.77, NS 🔹 G≥3 TRAEs: 54% vs 19% Outstanding discussion Prof. Levy @benlevylungdoc. https://t.co/w7SQ8w75QT

Academic & pragmatic phase III trial (PERSEE) #ESMO26 reshaping therapeutic choices for PD-L1 high patients (including ultra-high PD-L1 80/90%). Convincing & impressive results. Huge congrats to the GFPC group 🇫🇷 for leading this unique and crucial study! 👏@decroisette https://t.co/GhrgWTxf8Q

Pembrolizumab with or without platinum-based chemotherapy as first-line treatment in advanced NSCLC expressing PD-L1 ≥50%: The PERSEE randomized phase III trial (GFPC 01-2020) - Annals of Oncology https://t.co/QesNLpTc1q

#ESMO26 2614O PERSEE Head-to-head comparison of 1L treatments for NSCLC with PD-L1 ≥50% 📚Ann Oncol 2026 https://t.co/l4gbarp7a1 🔑Key Results 🎯 Population: 321 treatment-naïve advanced NSCLC patients with PD-L1≥50% and no driver mutations 📈 Median PFS: 16.1 months (Combo) vs 6.9 months (Mono) (HR 0.56, P<0.001) 🏆 ORR: 77.5% (Combo) vs 50.3% (Mono) ⏱️ Early progression rate (at 6 weeks): Drastically reduced with Combo (5.8%) vs Mono (26.5%) ⚠️ Grade ≥3 TRAEs: 54% (Combo) vs 19% (Mono)   🔥 The PFS benefit of Combo was maintained even in the ultra-high PD-L1 (90-100%) subgroup (25.4 vs 7.1 months)

Is more better in PD-L1 >50% PD-L1 NSCLC? 🇫🇷 PERSEE trial demonstrated that compared to pembro monotherapy, chemo-pembro showed better ORR and PFS, less early progressions, and numerically longer OS although not statistically significant (secondary endpoint, not powered). Really every patient needs chemo-IO? Is this the end of the discussion or just more data to debate? #ESMO26 #LCSM

Practice changing PERSEE trial. Chemo/IO vs IO in PDL1>50%. Trial powered for PFS, which was positive regardless of PDL1. OS not significant but favours chemo. More AEs with chemo. Hard to ignore these results but would’ve liked OS as primary. #LCSM #ESMO26 https://t.co/Al6qUUeocy

#ESMO26 | PERSEE For patients fit enough to tolerate chemotherapy, these results strengthen my preference for pembro + CT, even with very high PD-L1. The sustained PFS benefit and encouraging OS separation deserve attention. Heartfelt congratulations to the investigators for conducting this academic, multicentre trial addressing a question we face every day👏

🫁 PERSEE phase III: Pembro + chemo vs pembro alone in PD-L1 ≥50% NSCLC. 📈 PFS: 16.1 vs 6.9m (HR 0.56) OS: HR 0.77 (95% CI 0.57–1.05) 29.9vs50 mo ⚠️ Grade ≥3 TRAEs: 54% vs 19% Better disease control, numerical better OS. Patient selection key - practice informing #ESMO2026 https://t.co/OTWMrmzFVd

🚨 #ESMO26 | PERSEE phase III trial Dr Decroisette presents PERSEE, comparing pembrolizumab + chemo vs pembrolizumab alone in 1L advanced NSCLC with PD-L1 ≥50%. Numerically better PFS with the combination, but the primary endpoint was NOT met. The study was stopped prematurely, limiting its statistical power. 📉 Importantly, the pembrolizumab-alone arm substantially underperformed expectations in terms of PFS, raising important questions about the interpretation and generalisability of these findings. A numerically longer OS was also observed (50.2 vs 29.9 months), but the trial was not powered to demonstrate an OS difference. A thought-provoking study reminding us that numerical differences, statistical significance and clinical relevance are not always the same thing IMO #ESMOAmbassadors #ESMO26 #PERSEE #NSCLC #LungCancer

@myGFPC PRESEE trial is now presented by @decroisette #ESMO26. Publication in annals of oncology simultaneously ! So proup of our cooperative group 💪🇨🇵 https://t.co/ZnqX7HeAGH

⭐️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

Neoadjuvant MIBC Trials: KEYNOTE-866 (pembro) and ENERGIZE (nivo)negative. NIAGARA (durva) stands alone. Adjuvant is split too. ICI benefit in MIBC is real but marginal, and likely lives in a subset we have yet to identify. Utilit of chemo+IO less clear in EVP era. #ESMO26 https://t.co/1lIvphS2MF

🚨⭐ #ESMO26 | GU ONCOLOGY — DAY 1 HIGHLIGHTS @urologysummit A remarkable opening day in GU oncology — from perioperative immunotherapy to ctDNA, targeted therapy, and next-generation treatments. The strongest message for me? More treatment is not automatically better treatment. 🟠 1️⃣ KEYNOTE-866 | 4735O Perioperative pembrolizumab + gemcitabine/cisplatin did not significantly improve EFS in cisplatin-eligible MIBC. 📊 EFS HR 0.88 (95% CI 0.71–1.10), p=0.1366 pCR: 44.4% vs 35.8% 💡 A higher pathological response did not translate into a significant EFS benefit. 🟠 2️⃣ ENERGIZE | 4736O Perioperative nivolumab + chemotherapy also failed to meet its co-primary endpoints. 📊 EFS HR 0.94, p=0.6697 pCR: 39.1% vs 29.6% Another reminder that response endpoints must be interpreted alongside durable outcomes. 🟠 3️⃣ KEYNOTE-905 / KEYNOTE-B15 | 4733O / 4734O In exploratory KEYNOTE-905 analyses, EV + pembrolizumab favored surgery alone: ✅ OS HR 0.48 ✅ pCR 58.8% vs 25.3% with pembrolizumab alone and 10.3% with surgery alone In KEYNOTE-B15: 🧬 ctDNA clearance: 82.1% vs 66.7% with EV+pembro vs GC ctDNA positivity correlated with poorer EFS. Promising for risk stratification — but ctDNA-guided treatment still needs prospective validation. 🟠 4️⃣ TROPHY-U-01 Cohort 7 | 4742O SG + EV + zimberelimab in untreated metastatic urothelial cancer: ✅ ORR 81% ✅ Median PFS 19.3 mo ✅ Median DoR 16.7 mo ⚠️ Very promising, but phase Ib, only 21 patients, and substantial toxicity. 🔵 5️⃣ CAPItello-281 | LBA56 In PTEN-deficient de novo mHSPC: Capivasertib + abiraterone vs placebo + abiraterone ✅ Median OS 57.4 vs 46.5 mo HR 0.82 (95% CI 0.68–0.99) But the prespecified significance threshold was not met. An encouraging survival signal — not yet a formally established OS benefit. 🔵 6️⃣ THE NEXT FRONTIER IN PROSTATE CANCER ☢️ PSMA-targeted radioligand therapy 🧬 AR degraders & RIPTACs 💊 Next-generation ADCs 🔬 T-cell engagers & precision immunotherapy The challenge now is converting biological activity into durable benefit, manageable toxicity, and better patient selection. ⭐ MY POINT OF VIEW Three principles stood out today: ✅ Survival and metastasis-prevention endpoints matter ✅ Biomarkers must move from prognostic value to therapeutic guidance ✅ Novel combinations must justify both efficacy and toxicity The future of GU oncology is not simply intensification. It is smarter, biologically informed treatment selection. 🎯 Right strategy. Right patient. Right time. @gbanna74 @ravikanesvaran @neerajaiims @PGrivasMDPhD @Sebastiano_Buti @dmukherji @alison_tree @DrYukselUrun @yekeduz_emre @AgrawalTrush @ONCOassist @VuMedi @ProstateUK @OncologyNT @OncJournal #GUOncology #BladderCancer #ProstateCancer #MIBC #mHSPC #PrecisionOncology

🤩 @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

🚨 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

3. KRASCENDO-1 Divarasib Vs sotorasib or adagrasib, previously treated disease. OS 17.7m vs 12m. New SoC. NEJM 4. OptiTROP-Lung06 Sacituzumab tirumotecan + pembrolizumab in Chinese 1st line nonsquamNSCLC, PD-L1 <1%, without EGFR/ALK alterations. PFS 15m vs 5.7m. NEJM #ESMO26 https://t.co/OzWni3cnEZ

@Alfdoc2 The pembro-sac TMT in PDL1 negative NSCLC data is also stunning. The era of ADC (replacing chemo) has come.

🔥Lung🫁 #ESMO26 #LCSM 🎉Again🔂 4⃣ @NEJM 🎯DeLLphi-305 🎯OptiTROP-Lung06 🎯Krascendo 1 🎯SAFFRON 2⃣ @TheLancet 🎯PANKU-Lung01 🎯HERON-Lung01 3⃣ @Annals_Oncology 🎯PERSEE 🎯DeLLphi-304 🎯NEOTORCH 1⃣ @Nature 🎯NeoCOAST-2 1⃣ @NatureMedicine 🎯MDT-BRIDGE 1⃣ @JCO_ASCO 🎯Dalmelitinib Plus Aumolertinib @OncoAlert @Larvol @myESMO @IASLC @ASCO @EGFRResisters @KRASKickers @metcrusaders

OptiTROP-Lung06:🫁 Sac-TMT + pembrolizumab improved median PFS in PD-L1–negative advanced nonsquamous NSCLC (15.0 vs 5.7 months; HR 0.49), with fewer grade 3 or higher adverse events. OS remains immature; follow-up is key. @OncoAlert #ESMO26 #LungCancer #ESMOcommunity @myESMO https://t.co/nIAg7uYbdI

#ESMO26 Bispecific EGFRxHER3 targeting ADC IZA-BREN entering dynamic the #EGFR arena with the PANKU-Lung 01 trial post 3rd gen TKI: ✅ PFS 11,1 vs 5,7 m HR =0.4 ✅OS NR vs 19.4 data immature ✅ ORR 60.2 vs 34.5 ❌ Carbo+pem not SoC anymore , chemo+ami approved by FDA/EMA, SacTMT in FDA ( Optitrop Lung 06) ❓ How do those data compare with oncogene -driven approaches , like EGFR+MET in SAFFRON? #ESMOAmbassadors

#תשובות_לשאלות הסבר מופרט על המשמעות הקלינית של מחקר OptiTROP-Lung06 לבקשת @the_drow אז מה היה לנו עד עכשיו... בסרטן ריאות NSCLC לא-קשקשי עם PD-L1 מתחת ל-1%,ללא מוטציות מטרה ברות טיפול כגון EGFR או ALK, כבר שנים אנחנו תקועים באותו מקום: כימותרפיה + קיטרודה זה עובד, אבל לא חלקית... ה-PFS החציוני בדרך כלל סביב 5–7 חודשים, והחולים משלמים מחיר לא קטן ברעילות המטולוגית. בעיקר בגלל שהגידול לא מבטא מספיק PD-L1 ועד עכשיו לא היה לנו משהו טוב יותר להציע לחולים האילו כאן מחקר נכנס לתמונה OptiTROP-Lung06 במקום להוסיף עוד תרופה לכימותרפיה ה״רגילה״, הם שאלו שאלה אחרת: מה יקרה אם נחליף את אותה בתרופה חדישה ממשפחת ה-ADC? כלומר sacituzumab tirumotecan (TROP2 ADC) + קיטרודה, מול הסטנדרט הרגיל של כימותרפיה + קיטרודה. ובניתוח תוצאות הביניים במעקב של כ-9.7 חודשים, 455 חולים (בסין): PFS: 15 חודשים מול 5.7 חודשים (HR 0.49). זה לא שיפור קטן, זה יותר מכפול. אחוז התגובות היה כמעט זהה (50% מול 47%), אבל משך התגובה היה הרבה יותר ארוך 13.6 חודשים מול 6.8. היו גם יותר תגובות עמוקות. ב-OS עדיין מוקדם, אבל כבר רואים מגמה חיובית (HR 0.58), וב-12 חודשים 77.6% מול 66.4% עדיין חיים. כשהבטיחות/תופעות הלוואי של הטיפול החדש מפתיעו לטובה. פחות Grade ≥3 (47.6% מול 60.6%), ופחות רעילות המטולוגית משמעותית. יש יותר סטומטיטיס, אבל ברוב המקרים זה קל-בינוני. בקיצור לא רק יעיל יותר, אלא גם פחות "כבד" מבחינה המטולוגית מהכימו. אז מה זה אומר מבחינה קלינית? עד עכשיו, בחולים עם PD-L1 <1% לא באמת היה לנו משהו טוב יותר מכימותרפיה פשוטה + אימונתרפיה. מחקר OptiTROP-Lung06 מראה, שאפשר להחליף את הכימותרפיה ב-ADC ולקבל שליטה ארוכה יותר במחלה, עם פרופיל בטיחות סביר יותר מבחינת ספירת דם.

#ESMO26 | OptiTROP-Lung06 @NEJM Sac-TMT + pembrolizumab challenges first-line chemo-IO in PD-L1–negative nonsquamous NSCLC: • mPFS: 15.0 vs 5.7 mo; HR 0.49 • Grade ≥3 AEs: 47.6% vs 60.6% Impressive PFS benefit. OS remains immature—longer follow-up will be key. @OncoAlert @Larvol #esmo26

🇪🇸 #ESMO26 | Top Lung Abstracts 🫁 🚨 OPTITROP-Lung06: Phase III trial in PD-L1–negative, driver-negative nonsquamous NSCLC: 🔥 Median PFS: 15.0 vs 5.7 months 📉 HR 0.49 — 51% reduction in risk of progression/death 🎯 DOR: 13.6 vs 6.8 months 📊 12-mo OS: 77.6% vs 66.4% (immature data) ▶️ I wouldn’t call this a “chemo-free” regimen because the toxicity of an ADC is similar to chemo—> but this many be a potential option for this hard to treat PDL1 neg population. ▶️Could this change the 1L landscape? 👀maybe? but I would hope for a bigger survival advantage….data immature … #LungCancer #LCSM #ADC

🚨 Could ADCs replace chemotherapy in first-line NSCLC? Exciting results from Phase III OptiTROP-Lung06 at #ESMO26! Sacituzumab tirumotecan + pembrolizumab vs chemo + pembrolizumab in PD-L1-negative NSCLC: 📊 PFS: 15.0 vs 5.7 months ✅ Grade ≥3 AEs: 47.6% vs 60.6% OS data remain immature, but these results could change first-line treatment! #LungCancer @OncoAlert @weoncologists @OpenMedKate @StephenVLiu @GlopesMd @ManuelDomine

Big PFS gain in PD-L1-negative NSCLC. OptiTROP-Lung06 (LBA66): Randomized phase 3, 455 pts, 1L advanced nonsquamous NSCLC (PD-L1 TPS<1%, EGFR/ALK-negative): sac-TMT + pembro vs platinum/pemetrexed + pembro. mPFS 15.0 vs 5.7 mo (HR 0.49 (0.36–0.65), and OS HR 0.58 (0.38–0.88), still immature, but extremely promising! #ESMO26 #LCSM #OncTwitter https://t.co/ssgUKkif6S @OncoAlert @BalazsHalmosMD @ADesaiMD

Could OptiTROP-Lung06 be a practice-changing breakthrough in first-line PD-L1-negative NSCLC? #ESMO26 @myESMO https://t.co/DTm5Op2DUz https://t.co/zb4iyqHjlN

OptiTROP-Lung06 #ESMO26: 1L sac-TMT+pembro vs chemo-IO, PD-L1-neg nsq NSCLC ➡️ mPFS 15.0 vs 5.7 mo, HR 0.49 ➡️ ORR 50.2 vs 47.3%, mDOR 13.6 vs 6.8 mo ➡️ OS HR 0.58, immature ➡️ G≥3 TEAEs 47.6 vs 60.6% What must ADCs show to replace platinum? @LungCancerRx @OncoAlert @oncodaily https://t.co/5CoJUw2OIp

💍 THE GREAT PARTNER SWAP! OptiTROP-Lung06 | ESMO 2026 | LBA66 Pembrolizumab stays. Sac-TMT replaces chemotherapy! 🎯 PFS: 15.0 vs 5.7 mo | HR 0.49 📊 ORR: 50.2% vs 47.3% — similar! ⏳ DoR: 13.6 vs 6.8 mo — twice as long! ⚖️ Grade ≥3 AEs: 47.6% vs 60.6% 🔍 OS: HR 0.58 — immature; formal benefit unproven. The story? Similar responses, much longer disease control — with a different toxicity profile. Zhou F et al. NEJM. 2026. DOI: 10.1056/NEJMoa2611280 @myESMO @OncoAlert #ESMO26 #NSCLC #ADC #MVOnco

OptiTROP-Lung06 🫁 Sac-TMT + pembrolizumab: A substantial PFS benefit in 1L PD-L1-negative advanced NSCLC, with OS data still immature. @OncoAlert #ESMO26 #LungCancer #Lcsm #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/XTv3FAFHOZ

🔥🚨@OncoAlert Hot off the press. Just published @NEJM in conjunction with presentation @myESMO #ESMO26 results of: ⭐️#OptiTROP-#Lung06 phase 3 trial of: ❇️#Sacituzumab Tirumotecan (Sac-TMT)+ #Pembrolizumab Vs #Chemotherapy + #Pembrolizumab 🎯For #1stLine Tx of #PDL1 #negative (PD-L1 < 1%) advanced #NonSquamous non-small-cell #LungCancer (#NSCLC) WITHOUT genomic alterations. Study showed: ‼️Statistically significant & clinically meaningful ⬆️#ProgressionFreeSurvival Benefit. ✅ #mPFS 15.0 vs 5.7 mo (HR 0.49, p<0.001) ✅#ORR 50.2% and 47.3% ✅Immature #OS data; #HR: 0.49 P<0.001 ✅≥ Grade 3 #AEs: 47.6% vs 60.6% 👇🏻 https://t.co/SbNKX2ZOPm

🚨 #ESMO26 | OptiTROP-Lung06 (Phase III) Impressive PFS with sacituzumab tirumotecan + pembrolizumab vs chemotherapy + pembrolizumab in PD-L1-negative advanced non-squamous NSCLC: 📈 Median PFS: 15.0 vs 5.7 months 📈 12-month PFS: 51.1% vs 22.8% Could ADC + IO redefine first-line NSCLC treatment? Awaiting mature OS and safety data. #LungCancer #NSCLC

The response rates are close. The durability is not. OptiTROP-Lung06: first-line, PD-L1-negative, EGFR/ALK-negative nonsquamous NSCLC. Sac-TMT + pembrolizumab vs chemotherapy + pembrolizumab: • Primary BICR-PFS: 15.0 vs 5.7 months; HR 0.49; P<0.0001 • ORR: 50.2% vs 47.3% • Median response duration: 13.6 vs 6.8 months • Grade ≥3 TEAEs: 47.6% vs 60.6% OS is immature, and median follow-up is only 9.7 months. Could replacing conventional chemotherapy with a TROP2 ADC improve the durability of first-line disease control? Longer follow-up will be crucial. @StephenVLiu @CharuAggarwalMD @myESMO @OncoAlert #OptiTROPLung06 #ESMO26 #LCSM

Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus chemotherapy (chemo) plus pembrolizumab (P) as first-line (1L) treatment for PD-L1-negative advanced non-squamous (nsq) NSCLC: Randomized phase 3 OptiTROP-Lung06 study Caicun Zhou (CN) #ESMO2026 https://t.co/p4dZoOiEGI

Can we be Opti-mists about improving the outcome of the poorest prognosis subset of our patients w PD-L1 negative advanced NSCLC? Based on OptiTROP-Lung06 we should be! Sac-TMT/pembro sacked chemo/IO easily with much improved PFS, clear OS trends, better/different tox- only 5% discontinuation rate! (But note mucositis as common AE)

🚨 ESMO 2026 × NEJM: Is chemotherapy losing its place in first-line lung cancer? 🔥 OptiTROP-Lung06 delivers a striking Phase III result in PD-L1–negative advanced nonsquamous NSCLC! Sacituzumab tirumotecan + pembrolizumab vs chemo + pembrolizumab: 📊 Median PFS: 15.0 vs 5.7 months 🔥 51% lower risk of progression/death (HR 0.49) ✅ Grade ≥3 AEs: 47.6% vs 60.6% ⚠️ OS remains immature. The big question: Could TROP2-ADC + immunotherapy replace platinum chemotherapy in first line? Published simultaneously in NEJM during #ESMO26. @my_esmo @ESMO_open @ASCO @oncoalert #LungCancer #NSCLC #ESMO26

OptiTROP-Lung06 now @NEJM after #ESMO26 presentation showing Sac-TMT (TROP2 ADC) + pembro superior to standard chemotherapy + pembro. #ESMOAmbassadors @myESMO https://t.co/AWr8vi6VvR

Zhou: Optitrop-Lung06 chemo/io vs sacTMT/Pembro in PDL1 neg. Impressive PFS difference. Similar second line use. Deeper responses and double duration of response. Less tox except more stomatitis. Access is a major issue! #LCSM #ESMO26 https://t.co/Rqm8vvYalR

OptiTROP-Lung06; sacTMT v chemoIO(KN189); n455; open label; PFS HR 0.49; nearly 10m longer mPFS; females magnitude of benefit less; same ORR but double mDOR; tox profile looks interest in stomatitis + ocular. #ESMO26 https://t.co/ygTCgtwpzJ

🔥 Impressive results from OptiTROP-Lung06 at #ESMO26! Prof. Zhou presents phase III data in first-line PD-L1 TPS <1% advanced non-squamous NSCLC. 💥 Sac-TMT + pembrolizumab vs chemo + pembrolizumab: ✅ PFS: 15.0 vs 5.7 months HR 0.49 (95% CI 0.36–0.65), p<0.0001 📈 Encouraging OS trend: HR 0.58 (95% CI 0.38–0.88), but OS remains immature and exploratory at this interim analysis. A clearly positive PFS result and a promising OS signal. Longer follow-up and safety data will be essential to define its clinical impact. #ESMOAmbassadors #LungCancer #NSCLC #ADC

🫁 #ESMO2026 OptiTROP-Lung06: sac-TMT + pembro vs chemo + pembro in PD-L1-negative NSCLC in china. High never smoker (30%) and male (60%) popn. Promising PFS: 15.0 vs 5.7m (HR 0.49). OS immature. Global data awaited Sac-TMT is also in clinical trials at @NHSBartsHealth https://t.co/xL5qviAYhn

Sacituzumab Tirumotecan plus Pembrolizumab in PD-L1–Negative Advanced NSCLC | New England Journal of Medicine https://t.co/K430Ek0TOr

#ESMO26 | OptiTROP-Lung06 PD-L1 <1% non-sq NSCLC: Sac-TMT + pembro vs platinum/pem + pembro 🔹 PFS: 15 vs 5.7 mo (HR 0.49) 🔹 DoR: 13.6 vs 6.8 mo 🔹 OS: HR 0.58 (immature) 🔹 ≥G3 AEs: 47.6% vs 60.6% Strong results vs contemporary chemo-IO. https://t.co/mT1aoETKPQ

⭐️How do we improve outcomes for #lungcancer patients with PDL1 < 1% in the 1L setting? This may be addressed with the following two approaches 1⃣Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus chemotherapy (chemo) plus pembrolizumab (P) as first-line (1L) treatment for PD-L1-negative advanced non-squamous (nsq) NSCLC: Randomized phase 3 OptiTROP-Lung06 study 2⃣First-line (1L) olomorasib + chemoimmunotherapy (chemo-IO) in KRAS G12C-mutant NSCLC: Updated results from the LOXO-RAS-20001 and SUNRAY-01 trials. These are separate strategies (ADC vs TKI), but both address a fundamental need which is combination approaches for certain subsets of 1L NSCLC. @lcsmchat @OncoAlert @OncLive @Onco_Nexus @LungCancerEu @Lung_Cancers @LungCancerRx @MedwatchHQ @YoungLungCancer @KRASKickers

🚨 #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

Immunotherapy in breast cancer: why patient selection matters. Reflections on KEYNOTE-B49 from #ESMO26. PD-L1 is assessed using CPS, not a simple percentage. @myESMO #bcsm https://t.co/MKkSpTpi3Z https://t.co/5g4rOH6hmL

#keynoteB49- @myESMO #ESMO26 Adding ICB/ immunotherapy in advanced HR+ #breastcancer - wishful thinking 🤔 this context is immune deplete! -PFS 6-6.7 mo ➡️ Early high grade immune + HR + BC is the right place for it #ESMOAmbassadors https://t.co/nTuY30fwfU

PFS-positive. But is that enough to change practice? KEYNOTE-B49: after endocrine therapy in PD-L1 CPS ≥1 HR+/HER2− advanced breast cancer, pembrolizumab + chemotherapy met its primary PFS endpoint: • Median PFS: 6.7 vs 6.0 months; HR 0.74 • Final OS: 21.0 vs 22.2 months; HR 1.04 — no significant improvement • Grade ≥3 treatment-related AEs: 37.6% vs 32.7% The PFS result is statistically positive. The clinical decision is harder. Does this benefit justify adding immunotherapy for the broad CPS ≥1 population—or do we need better selection? @hoperugo @stolaney1 @myESMO @OncoAlert #KEYNOTEB49 #ESMO26 #BCSM

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

🔹Small improvement in mPFS with pembrolizumab (vs placebo) + chemotherapy in the KN-B49 ph3 study for endocrine resistant, PDL1+ (CPS≥1) HR+/HER2- MBC 🔹Bigger difference in CPS≥10: small numbers and a secondary endpoint 🔹No OS difference #ESMO2 #ESMOAmbassadors @myESMO https://t.co/7swgsAylw8

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

KEYNOTE B-49: Chemo +/- pembro in PDL1+ (CPS≥1) HR+ MBC 79% CPS 1-9 53% recv'd capecitabine PFS: 6.7 vs 6.0 mo HR 0.74 OS: HR 1.04 PFS CPS≥10 :7.5 vs 4.4 HR 0.59 @OncoAlert @hoperugo #ESMO26 https://t.co/ZyCmtddjJq

#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.

Honoured to have had the opportunity to present "Optimal induction treatment in non-metastatic bladder cancer" at #ESMO26 in Madrid! 🚨 Does a deeper pathological response translate into greater survival benefit in perioperative MIBC? An intriguing pattern across four phase III trials: 🔹 NIAGARA: ΔpCR +10 pp | EFS HR 0.68 🔹 KEYNOTE-B15: +23 pp | HR 0.53 🔹 VOLGA: +32 pp | HR 0.51 🔹 KEYNOTE-905: +49 pp | HR 0.40 Larger absolute pCR gains appear to track with greater EFS benefit. But the comparator matters! KEYNOTE-905 and VOLGA used surgery-based controls without neoadjuvant systemic therapy (control "pCR" ~8–9%), whereas NIAGARA and KEYNOTE-B15 used active neoadjuvant cisplatin-based chemotherapy. Thus, the magnitude of ΔpCR is not directly comparable across trials. The key question: Can pCR, combined with utDNA + ctDNA clearance, become a reliable tool for response-adapted treatment intensity? ⚠️ This is an exploratory, trial-level observation—not proof that pCR improvements cause EFS benefits or that pCR is a validated surrogate endpoint! Better biomarkers could help us maximize cure while minimizing overtreatment. 🔬 #ESMO26 #BladderCancer @weoncologists @urotoday @Uromigos @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

9, 9, and 3. 💉 VOLGA out tonight in @NEJM — perioperative MIBC now has three winning EV regimens: EV-303: EV ×9 (3 pre + 6 post-cystectomy) → EFS HR 0.40 · OS HR 0.50 EV-304: EV ×9 (4 pre + 5 post) → EFS HR 0.53 · OS HR 0.65 VOLGA: EV ×3 — all preop, zero after surgery → EFS HR 0.51 · OS HR 0.58 ⅓ the vedotin. Most of the efficacy. 🧵 @myESMO @OncoAlert

🚨⭐ #ESMO26 | GU ONCOLOGY — DAY 1 HIGHLIGHTS @urologysummit A remarkable opening day in GU oncology — from perioperative immunotherapy to ctDNA, targeted therapy, and next-generation treatments. The strongest message for me? More treatment is not automatically better treatment. 🟠 1️⃣ KEYNOTE-866 | 4735O Perioperative pembrolizumab + gemcitabine/cisplatin did not significantly improve EFS in cisplatin-eligible MIBC. 📊 EFS HR 0.88 (95% CI 0.71–1.10), p=0.1366 pCR: 44.4% vs 35.8% 💡 A higher pathological response did not translate into a significant EFS benefit. 🟠 2️⃣ ENERGIZE | 4736O Perioperative nivolumab + chemotherapy also failed to meet its co-primary endpoints. 📊 EFS HR 0.94, p=0.6697 pCR: 39.1% vs 29.6% Another reminder that response endpoints must be interpreted alongside durable outcomes. 🟠 3️⃣ KEYNOTE-905 / KEYNOTE-B15 | 4733O / 4734O In exploratory KEYNOTE-905 analyses, EV + pembrolizumab favored surgery alone: ✅ OS HR 0.48 ✅ pCR 58.8% vs 25.3% with pembrolizumab alone and 10.3% with surgery alone In KEYNOTE-B15: 🧬 ctDNA clearance: 82.1% vs 66.7% with EV+pembro vs GC ctDNA positivity correlated with poorer EFS. Promising for risk stratification — but ctDNA-guided treatment still needs prospective validation. 🟠 4️⃣ TROPHY-U-01 Cohort 7 | 4742O SG + EV + zimberelimab in untreated metastatic urothelial cancer: ✅ ORR 81% ✅ Median PFS 19.3 mo ✅ Median DoR 16.7 mo ⚠️ Very promising, but phase Ib, only 21 patients, and substantial toxicity. 🔵 5️⃣ CAPItello-281 | LBA56 In PTEN-deficient de novo mHSPC: Capivasertib + abiraterone vs placebo + abiraterone ✅ Median OS 57.4 vs 46.5 mo HR 0.82 (95% CI 0.68–0.99) But the prespecified significance threshold was not met. An encouraging survival signal — not yet a formally established OS benefit. 🔵 6️⃣ THE NEXT FRONTIER IN PROSTATE CANCER ☢️ PSMA-targeted radioligand therapy 🧬 AR degraders & RIPTACs 💊 Next-generation ADCs 🔬 T-cell engagers & precision immunotherapy The challenge now is converting biological activity into durable benefit, manageable toxicity, and better patient selection. ⭐ MY POINT OF VIEW Three principles stood out today: ✅ Survival and metastasis-prevention endpoints matter ✅ Biomarkers must move from prognostic value to therapeutic guidance ✅ Novel combinations must justify both efficacy and toxicity The future of GU oncology is not simply intensification. It is smarter, biologically informed treatment selection. 🎯 Right strategy. Right patient. Right time. @gbanna74 @ravikanesvaran @neerajaiims @PGrivasMDPhD @Sebastiano_Buti @dmukherji @alison_tree @DrYukselUrun @yekeduz_emre @AgrawalTrush @ONCOassist @VuMedi @ProstateUK @OncologyNT @OncJournal #GUOncology #BladderCancer #ProstateCancer #MIBC #mHSPC #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

#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

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

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?

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

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

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

🧑‍🔬I recently posted data from G-HOPE-001 and CLARITY-Gastric01, two phase 3 trials evaluating their respective ADCs in previously treated CLDN18.2-positive gastric, GEJ, or esophageal adenocarcinoma. 🧐 Can you spot the differences between arcotatug tavatecan and sonesitatug vedotin? Btw, pay attention to the interesting design trade-off between retaining versus silencing the antibody’s Fc region. 😲Non-Fc-silenced ADCs (sonesitatug vedotin): Because ADCC and CDC provide an additional mechanism of tumor-cell killing, this ADCs may retain activity even in tumors with lower levels of CLDN18.2 expression. - Trade-off: Preserving Fc activity may also increase the potential for immune-mediated toxicity, particularly because normal gastric mucosa expresses CLDN18.2. 🤐Fc-silenced ADCs (arcotatug tavatecan): Without additional ADCC/CDC-mediated killing, the ADC depends more heavily on target binding, internalization, and intracellular payload release. As a result, higher levels of CLDN18.2 expression may be needed to achieve sufficient payload delivery and tumor-cell killing. --- -ADC (Antibody-Drug Conjugate) -ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity) -CDC (Complement-Dependent Cytotoxicity) -Fc (Fragment Crystallizable region) -ILD (Interstitial Lung Disease) #GastricCancer #CLDN182 #ESMO26 #GIOnc

🍽️ #ESMO26 CLARITY-Gastric01 (ph III): CLDN18.2 ADC sonesitatug vedotin improved OS in pretreated gastroesophageal cancer. ≥3L: 10.0 vs 5.0 mo (HR 0.47) ≥2L: 10.6 vs 6.4 mo (HR 0.58) Key caveat: central-review PFS endpoint not met. #gicsm https://t.co/8c5OCP2cPD

CLARITY-Gastric01 at #ESMO2026: a significant overall survival benefit with sonesitatug vedotin (Sone-Ve), a CLDN18.2-targeted ADC, in previously treated advanced gastroesophageal cancer. This global phase III trial compared Sone-Ve with investigator’s choice of therapy: • Third line and beyond: Median OS 10.0 vs 5.0 months, HR 0.47 (95% CI 0.36–0.62), meeting the primary OS endpoint. • Overall second-line-and-beyond population: Median OS 10.6 vs 6.4 months, HR 0.58 (95% CI 0.47–0.73), a key secondary endpoint. • PFS by blinded central review did not reach statistical significance: 4.2 vs 3.8 months, HR 0.77. Understanding the OS–PFS discordance remains important. • Safety: Grade ≥3 treatment-related adverse events occurred in 36.4% vs 44.8%, although grade ≥3 gastrointestinal toxicity was higher with Sone-Ve: 11.1% vs 6.3%. Testing thresholds matter: Enrollment required CLDN18.2 membranous staining in ≥25% of tumor cells at any intensity, making it much broader. Zolbetuximab eligibility uses ≥75% with moderate-to-strong staining. “CLDN18.2-positive” needs an assay-specific, treatment-specific definition. #GastricCancer #GIOncology #PrecisionOncology

🔥 CLARITY-Gastric01 - Phase 3 (AstraZeneca release, ESMO LBA7) 🎯 Previously treated (≥2L) CLDN18.2+ gastric, GEJ or oesophageal adenocarcinoma - How positive, you may ask? Not the usual 75%, but rather 25% expression. 💊 Sonesitatug vedotin (CLDN18.2 ADC) vs investigator's choice 👥 532 patients ✅ 3L+ OS 10.0 vs 5.0 mo, HR 0.47 ✅ ITT OS 10.6 vs 6.4 mo, HR 0.58 ➖ PFS co-primary missed, HR 0.77, p=0.053 ⚠️ 2L-only OS HR 0.88, CI crosses 1 ⚠️ Prior zolbetuximab exposure, if any, not reported In 3L+, mOS doubles from 5 to 10 months, in a population defined at 25% CLDN18.2 expression, far broader than the zolbetuximab cut-off. Now read the second line carefully: PFS missed, and the second-line OS HR was 0.88 with a CI crossing 1, so the ITT result leans on later lines. Let’s please approve this already, at least for 3L. 🙏 But wait!! What can be said about patients with prior exposure to zolbetuximab ??? Also, G-HOPE-001 (see below), selected patients at a much stricter threshold (2+ in 75% or more), so do not compare the hazard ratios head to head. The open question for both ADCs is activity after first-line zolbetuximab. #GastricCancer #CLDN182 #ESMO26 #GIOnc https://t.co/m8KiNVjjLL

#ESMO26 CLARITY-Gastric 01 (CG-01): A phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) by Rui Hua Xu https://t.co/dSCSuu8cx8

Promising results from the Phase III CLARITY-Gastric01 trial, presented at ESMO 2026. Sonesitatug vedotin, an investigational CLDN18.2-targeted antibody–drug conjugate, improved median overall survival from 5.0 to 10.0 months in patients receiving third-line or later treatment for advanced gastro-oesophageal cancer (HR 0.47). In the broader population receiving second-line or later treatment, median survival improved from 6.4 to 10.6 months. The trial did not meet its progression-free survival endpoint, but the overall survival findings are encouraging for patients with limited treatment options. #GastricCancer #Oncology #CancerResearch #ClinicalTrials #ESMO26 https://t.co/2DRhlAoPjN

🚨 #ESMO26 | CLARITY-Gastric01 Phase III Sonesitatug vedotin in CLDN18.2+ gastric/GEJ cancer: ✅ 3L+ OS: 10 vs 5 mo (HR 0.47) ✅ ITT OS: 10.6 vs 6.4 mo ✅ ORR: 23.3% vs 13.8% ⚠️ ITT PFS not significant (p=0.053) 🎯 Promising new ADC in gastric cancer! #GastricCancer #ADC https://t.co/MUINCaFIkK

ツチノコ的ESMOレビュー⑪ 胃がんのもう一つのCLDN18.2を狙うADCです。 今回はこちら、 「CLARITY-Gastric01」 CLDN18.2を狙うADC 「sonesitatug vedotin」 （ソネシタツグ ベドチン） の第Ⅲ相試験です。 （これCLDN系は抗体はtug系っぽいですね。） ツチノコ的ESMOレビュー④のArcotatug tavatecanのライバルになります。 https://t.co/0JWvQ5K8Vo がん細胞の表面にあるCLDN18.2という目印を見つけて、抗がん剤を届ける治療は一緒です。 搭載している爆弾は「MMAE」。 細胞分裂に必要な微小管の働きを邪魔する薬ですね。 ADCといえばトポイソメラーゼⅠ阻害薬を搭載したものが目立ちますが、こちらは違うタイプです。 今回の対象は、すでに治療を受けた進行胃がんなどの患者さん。 二次治療以降で、Sone-Ve単剤と医師が選択した治療を比較しました。 結果は、、 主要評価項目である三次治療以降の全生存期間が、 Sone-Ve：10.0か月 対照群：5.0か月 HR 0.47、p＜0.000001。 生存期間の中央値が約2倍となっています。 さらに、二次治療以降の全体532人でも、 Sone-Ve：10.6か月 対照群：6.4か月 HR 0.58、p＜0.000004。 これは注目したい結果ですね。 そして、もう一つ面白いのが、、 CLDN18.2の条件が、 「染色の強さを問わず、腫瘍細胞の25%以上に発現」 だったこと。 発現が25%以上75%未満の群でも、OSのHRは0.63でした。 強く発現している患者さんだけでなく、対象を広げられる可能性があります。 ただし、ここで一つ大事な点があります。 もう一つの主要評価項目である、中央判定の無増悪生存期間は、 4.2か月 vs 3.8か月 HR 0.77、p＝0.053。 こちらは統計学的有意差に届いていません。 つまり、、 「がんが進行するまでの期間では有意差がつかなかったが、全生存期間は延長した」 という結果です。 ここは気になります？？ ライバルのArcotatug tavatecanはPFSでも効果を示したのでこれは難しい。 後治療の影響や画像評価の違いなど、なぜこの乖離が生じたのかは詳細を確認したいところです。 ただし、Arcotatug tavatecanはCLDN75%以上陽性なので対象選択の問題もあるかもしれません。 Grade 3以上の治療関連有害事象は、 36.4% vs 44.8%。 少なくとも、重い副作用が増えて得られた生存期間の延長という結果ではありません。 副作用パラメータは追えてませんが、同じ薬剤の他の発表で悪心が6%ほどなのでArcotatug tavatecanの方がやや使いやすいかも？？ 使い分けとしてはCLDN陽性75%以上はArcotatug tavatecan それ以外はsonesitatug vedotinみたいな感じ？？ 少なくともADCが標準治療にはなりそうですが、これも1次治療にどうせ上がってきそうなので 今後の使い分けも非常に大事かなと思います。 Sonesitatug vedotin reduced the risk of death by 42% in 2nd- and later-line CLDN18.2-positive advanced gastric/GEJ cancers in CLARITY-Gastric01 - AstraZeneca https://t.co/CouYIPpwrz

📣 Second Presidential Symposium #ESMO26 👉🏽 CLARITY-Gastric 01 (CG-01): phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2)-positive gastroesophageal carcinoma (GEC) 🗣️ Discussed by @salahAlBatran 📌 PFS 4.1 vs 2.7m HR 0.56 (3+L) 📌 OS 10 vs 5m HR 0.47 (3+L) ☣️ Most frequent GI, decreased appetite and hematologic ☣️ Grade 3 or higher 36.4% @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @NEJM @brunolarvol 👇🏽👇🏽

🚨🎗️ ESMO26 | CLARITY-Gastric01 – Fase III Sonesitatug vedotina (ADC anti-CLDN18.2) vs. tratamento padrão no câncer gastroesofágico avançado CLDN18.2 positivo. ✅ Sobrevida global em 3ª linha ou mais: 10,0 vs. 5,0 meses (HR 0,47) ✅ 53% de redução no risco de morte ✅ Sobrevida global na população total: 10,6 vs. 6,4 meses (HR 0,58) ✅ Resposta objetiva: 23,3% vs. 13,8% ⚠️ PFS na população total não atingiu significância estatística. 🎯 Potencial novo padrão terapêutico, especialmente a partir da terceira linha, com ganho expressivo de sobrevida. #ESMO26 #CLARITYGastric01 #SonesitatugVedotin #GastricCancer #CLDN182

🎯 #ESMO26 CLARITY-Gastric01 (ph III): sone-ve (CLDN18.2 ADC) vs TPC in 2L+ gastric/GEJ with CLDN18.2 ≥25% (any intensity) 📈 3L+ OS 10.0 vs 5.0 mo (HR 0.47) 📈 ITT OS 10.6 vs 6.4 mo (HR 0.58); 2L HR 0.88 🧬 Benefit at ≥75% and 25–74% expression ⚠️ Less heme tox, more GI tox https://t.co/0n6cZfKqh5

🔥Presidential session at ESMO 2026 🔥 CLARITY-Gastric 01: Ph 3 of sonesitatug vedotin in 2L+ CLDN18.2-positive GEC #ESMO26 #ESMOAmbassadors 👉ORR: 23 vs 13% 👉mPFS: 4.2 vs 3.8 mo 👉mOS: 10 vs 5 mo 👉No new safety signals 🧐 exciting results, new option for 2L+ CLDN18.2+ pts @myESMO @ASCO

🚨 #ESMO26 Plenary | #CLARITYGastric01 Sonesitatug vedotin significantly improves OS in CLDN18.2+ advanced gastric/GEJ cancer! Median OS:
- 3L+: 10 vs 5 months (HR 0.47)
- 2L+: 10.6 vs 6.4 months (HR 0.58) 💥 Potential new standard of care! @OncoAlert #GastricCancer @myESMO https://t.co/84HELwsuNf

As co-author, excited to share CLARITY-Gastric01 data. Sone-Ve showed a meaningful survival benefit for pts with previously treated CLDN18.2-positive GC/GEJ cancers, reinforcing CLDN18.2 as a key therapeutic target beyond the frontline setting. #ESMO2026 #GIOncology https://t.co/P1Y1RqW4i2

#ESMO26 | CLARITY-Gastric01 Doubling OS from 5 to 10 months with the CLDN18.2-targeted ADC sonesitatug vedotin in ≥3L is impressive (HR 0.47). Benefit even in patients with lower CLDN18.2 expression is encouraging. However, the primary PFS endpoint was not met in the ITT population. Its role in 2L and efficacy after zolbetuximab remain unclear. one question: Given that CLDN18.2 expression can change after treatment, should a fresh biopsy have been mandatory at study enrollment? Or does lowering the positivity cutoff to ≥25% reduce the clinical relevance of this discordance, making archival tissue sufficient?

#ESMO26 🚀 CLARITY-Gastric01 | Phase III 🧬 CLDN18.2+ GEC | Sone-Ve vs SOC 🏆 OS benefit: 🔹 3L+: 10.0 vs 5.0 mo (HR 0.47) 🔹 2L+: 10.6 vs 6.4 mo (HR 0.58) 🎯 ORR: 23.3% vs 13.8% ⚠️ PFS: HR 0.77 (NS) ✅ G≥3 TRAEs: 36.4% vs 44.8% 💡 Potential new SOC in 2L+! @OncoAlert https://t.co/Rx8rIGBoS8

🆙#ESMO26 Presidential Symposium II 🔥CLARITY-Gastric 01 (CG-01): A Phase 3 Study of Sonesitatug Vedotin (Sone-Ve) in Second or Later-Line (2L+) Advanced or Metastatic Claudin 18.2 (CLDN18.2)-Positive Gastroesophageal Carcinoma (GEC) 🎙️Dr. Rui-Hua Xu 🔢LBA7 🎯Significantly Improved OS: 3L+ 10.0 vs 5.0mo (HR 0.47, p<0.001); ITT 10.6 vs 6.4mo (HR 0.58, p<0.001; n=532) 🎯PFS Not Significant (HR 0.77, p=0.05) 🎯Grade≥3 TRAEs 36.4% vs 44.8% ☑️NCT06346392 🔗 https://t.co/bIUj6lFjno @OncoAlert @Larvol @myESMO

4 studies I’m watching today at #ESMO26 Presidential Symposium II (16:30 CET): KRAScendo 1, SAFFRON, CLARITY-Gastric 01 and HARMONi-GI1. Which one are you waiting for? I’ll post notes right after each LBA. #Oncology https://t.co/2qVqWcF773

ESMO 2026 Presidential2 | CLARITY-Gastric 01: Phase III: Sonesitatug vedotin vs investigator's choice in previously treated CLDN18.2+ advanced gastroesophageal cancer (n=532). 📊 Key results: ✅ 3L+ median OS: 10.0 vs 5.0 months (HR 0.47; p<0.001) ✅ 2L+ median OS: 10.6 vs 6.4 months (HR 0.58; p<0.001) ⚠️ Median PFS: 4.2 vs 3.8 months (HR 0.77; p=0.05) — did not meet statistical significance threshold. ✅ Grade ≥3 TRAEs: 36.4% vs 44.8% 🔥 53% reduction in risk of death in 3L+! Notably, OS benefit was observed even with lower CLDN18.2 expression (≥25% to <75%). A striking OS benefit despite a modest, statistically nonsignificant PFS improvement. Could this ADC redefine later-line treatment of gastric cancer? @myESMO @OncoAlert #ESMO26 #GastricCancer #ADC

After progression on a CDK4/6 inhibitor, what next? My #ESMO26 reflections on FOURLIGHT-1 and investigational selective CDK4 inhibition. @myESMO @OncoAlert #bcsm Professional enquiries: https://t.co/MKkSpTpi3Z https://t.co/5YRPIBZdKl

FOURLIGHT-1: HR+/HER2− breast cancer after CDK4/6i. Atirmociclib + fulvestrant met the phase II PFS endpoint: 9.4 vs 6.6 months; HR 0.60. Control: fulvestrant OR everolimus/exemestane. Separate superiority over the latter was not shown. #FOURLIGHT1 #ESMO2026 #BCSM

@BianchiniGP @antgiorda Kudos to the team. 9.4 vs 6.6 months median PFS post-CDK4/6i deserves attention, though investigator-assessed endpoints in a Phase II warrant caution. I would hold on implications until the Phase III. Look forward to FOURLIGHT-3. #ESMO26

🔥 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

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

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