Physician discussion, Days 1–2

Physician posts on X, October 23–24.

DASL-HiCaP (posts), FOURLIGHT-1 (posts) and KEYNOTE-B49 (posts) also drew heavy physician discussion. See the DASL-HiCaP and KEYNOTE-B49 trial pages for full results and physician reactions; FOURLIGHT-1 posts are on the ESMO 2026 trials page.

Lung cancer

DeLLphi-305: tarlatamab + durvalumab as first-line maintenance in ES-SCLC

Phase 3, N=563: tarlatamab (IMDELLTRA, Amgen) plus durvalumab vs durvalumab alone after first-line chemo-immunotherapy. Median OS 21.1 vs 12.7 months, HR 0.42 (95% CI 0.32–0.54), P<0.001, at a prespecified interim analysis. 12-month OS 79.4% vs 53.3%. PFS 7.4 vs 1.9 months, HR 0.34 (0.28–0.42). ORR 26.4% vs 4.1%. (ESMO 2026 LBA3, Jacob Sands; NEJM; data cutoff Jul 7, 2026) Grade ≥3 TEAEs 46.8% vs 40.6%. CRS 49.6%, grade 3 0.4%, no grade 4 or 5. ICANS 1.1%, none grade ≥3. (LBA3 abstract and slides) The first-line combination is investigational. Tarlatamab has full FDA approval for ES-SCLC that progressed on or after platinum chemotherapy (November 19, 2025). (KOL Pulse DeLLphi-305 page)

Physicians called it a new standard. The questions raised were cost, toxicity outside trials, access to tarlatamab, and the low complete response rate.

The most detailed critical post came from Misty Dawn Shields, a translational SCLC oncologist at Indiana University, after the presentation. She called the OS improvement unprecedented and raised four concerns: access to tarlatamab at progression for patients in the control arm, whether the benefit reflects synergy or additivity (1L maintenance vs second line), patient selection and the need for predictive biomarkers, and treatment options after progression on the combination.

The critical perspective

Misty Dawn Shields @drshieldsmd

translational thoracic oncologist (MD, PhD), Indiana University; founder, SCLC SMASHERS · Oct 25

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.

Read the full post on X ↗

Masahiro TORASAWA, MD. PhD. @M_Torasawa

thoracic oncologist, Juntendo University · Oct 25

"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

View post on X ↗

DeLLphi-305 trial page · All physician posts on DeLLphi-305 at ESMO 2026

Melanoma

INTerpath-001: an individualized mRNA vaccine plus adjuvant pembrolizumab

Phase 3, N=1,137, resected stage IIB–IV melanoma: intismeran autogene (V940/mRNA-4157, Moderna and Merck) plus pembrolizumab vs placebo plus pembrolizumab. RFS HR 0.58 (95% CI 0.45–0.75); 24-month RFS 82.2% vs 70.0%. DMFS HR 0.62 (0.45–0.85). OS is immature and did not meet its significance boundary: HR 0.77 (0.45–1.31), P=0.33. (ESMO 2026 LBA1, Georgina V. Long; data cutoff Jun 30, 2026; median follow-up 24.6 months) All-cause grade 3–5 AEs 23.6% vs 20.3%. All-cause AEs led to death in 8 (1.1%) vs 0 patients; 2 (0.3%) vs 0 were treatment-related, none related to intismeran. (LBA1 AE summary slide) Intismeran is investigational.

Physicians called the result positive. They debated the comparator (adjuvant pembrolizumab alone, when SWOG S1801 and NADINA moved immunotherapy before surgery), the deaths in the experimental arm, and tissue requirements.

Agreement and debate

Nicholas Hornstein @GIMedOnc

GI medical oncologist, Northwell · Oct 23

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

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Mario Balsa @MarioBalsaMD

medical oncologist, melanoma, Hospital Clínic Barcelona · Oct 23

🚨 #ESMO26 | Phase III INTerpath-001 🚨 After an early embargo breach, @myESMO brought the abstract release forward!!!!!! And yes, it’s clearly positive: 📉 RFS HR 0.58 📉 DMFS HR 0.62 But here’s the uncomfortable part: SWOG S1801 also reported an HR 0.58…simply by moving 3 doses of pembrolizumab BEFORE surgery… ☝🏼Not the same population. Not the same endpoint. Not a cross-trial comparison. Still, in 2026, should a personalized mRNA vaccine really be benchmarked against adjuvant pembro alone? Before calling this a new standard, I want to see the vaccine face the NEOADJUVANT era. Same HR. Different path. And that may be the real INTerpath question 👀 @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma What do you think? @SuyogCancer @OncBrothers @A_May_MD @Dr_R_Kurzrock

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Yakup Ergün @dr_yakupergun

medical oncologist · Oct 24

#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.

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Daniel Heng @DrDanielHeng

GU medical oncologist · Oct 24

#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

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INTerpath-001 trial page · All physician posts on INTerpath-001 at ESMO 2026

Bladder cancer

VOLGA: durvalumab + 3 cycles of neoadjuvant EV, cisplatin-ineligible MIBC

Phase 3, N=695, cisplatin-ineligible or refusing. Durvalumab + EV vs control: EFS HR 0.51 (95% CI 0.38–0.67), 24-month EFS 64% vs 45%. OS HR 0.58 (0.40–0.83), 24-month OS 78% vs 69%. pCR 45% vs 10% (local review). The triplet arm with tremelimumab: EFS HR 0.61 (0.47–0.80); OS HR 0.77 (0.54–1.07), not significant. Grade 3–4 AEs 64% (durvalumab + EV), 70% (triplet), 44% (control). (ESMO 2026 LBA2, Tom Powles; data cutoff Mar 2, 2026) Investigational. FDA granted Priority Review to durvalumab + EV on September 25, 2026. (KOL Pulse VOLGA page)

Physicians favored the doublet. The debate was the triplet’s added toxicity and how much EV is needed, since VOLGA gave no adjuvant EV.

The doublet vs the triplet

Tom Powles @tompowles1

GU oncologist; VOLGA presenter · Oct 24

VOLGA also explored short periods of EV with duvalumab and tremelimumab in muscle invasive bladder cancer #ESMO26 @NEJM. Results showed EVDT improved EFS vs cystectomy (HR 0.61). Significant OS was not reached at this interim (HR 0.77 -ongoing analysis). EVDT = 10% higher rates of G3/4 toxicity and less EV delivery than the EV durvalumab arm. More is not always better. It appears the addition of treme partly compromised delivery of EV, which likely accounts for the more modest results compared to the doublet @OncoAlert

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Shilpa Gupta @shilpaonc

GU oncologist, Cleveland Clinic · Oct 24

Kudos @tompowles1 on a fantastic #VOLGA presidential @ #ESMO26 👏 Less is More! • Cis-inelig MIBC, 25% were cis refusers
• D+EV x3 → RC → adj D x9 (NO adj EV)
• EFS HR 0.51 
• OS HR 0.58 
• pCR 45 vs 10%
• G3-4 TRAE 30%, 
• neuropathy only 18% 
• imAEs 33% (G3-4 11%)
• GHS/QoL maintained post-RC • Treme ↑tox (G3-4 42%, 5 deaths), NO OS gain. My take: it's not just about chasing bigger numbers. Tox matters too, especially when OS is achieved. Need to discuss the pros and cons with patients. Less PN and skin tox, and fewer G3+ immune AEs than more cycles and that's a win for patients ! 🙌 @Uromigos @OncoAlert @brian_rini @LosUromigos @drenriquegrande

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Adam B. Weiner, MD @Adam_Weiner535

urologic oncologist, Cedars-Sinai · Oct 24

🚨 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

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VOLGA trial page · All physician posts on VOLGA at ESMO 2026

KEYNOTE-866 and ENERGIZE: two negative Phase 3 trials of PD-1 + cisplatin chemotherapy

Both trials added a PD-1 inhibitor to neoadjuvant gemcitabine-cisplatin, continued after cystectomy, in cisplatin-eligible MIBC. KEYNOTE-866 (pembrolizumab, N=907): EFS HR 0.88 (95% CI 0.71–1.10), one-sided P=0.1366, not significant. OS HR 1.00 (0.79–1.27). pCR 44.4% vs 35.8%; OS and pCR were not formally tested. (ESMO 2026 4735O, Jens Bedke; data cutoff Jan 26, 2026) ENERGIZE (nivolumab, N=653): EFS HR 0.94 (0.72–1.24), P=0.6697. pCR 39.1% vs 29.6%, not significant after multiplicity adjustment. Both co-primary endpoints were missed. (ESMO 2026 4736O, Andrea Necchi; median follow-up 54.5 months) Neither regimen is approved for MIBC. NIAGARA, with durvalumab on the same chemotherapy backbone, was positive.

Physicians noted that higher pCR did not translate into EFS. Explanations offered for the difference from NIAGARA included control-arm outcomes and the need for biomarker selection.

KEYNOTE-866 trial page · All physician posts on KEYNOTE-866 at ESMO 2026

ENERGIZE trial page · All physician posts on ENERGIZE at ESMO 2026

KEYNOTE-B15 / EV-304: ctDNA from the approved perioperative EV + pembrolizumab regimen

Exploratory ctDNA analysis (Signatera) presented by Jonathan Chatzkel. ctDNA clearance from baseline to surgery 82.1% vs 66.7% with EV + pembrolizumab vs gemcitabine-cisplatin. ctDNA-positive after surgery 4.8% vs 13.5%. pCR 72.4% vs 43.7% in patients ctDNA-negative before surgery, and 3.7% vs 2.2% in those still ctDNA-positive. ctDNA-positive status was associated with worse EFS in both arms. (ESMO 2026 Abstract 4734O and slides; discussant slide for pCR by ctDNA; data cutoff Oct 27, 2025) ctDNA is not validated to guide treatment. Perioperative EV + pembrolizumab has been FDA approved for MIBC since July 10, 2026, based on the trial’s EFS and OS results. (KOL Pulse KEYNOTE-B15 page)

Physicians agreed ctDNA is prognostic. The open question is whether ctDNA and pCR can guide de-escalation, including adjuvant EV and bladder sparing.

KEYNOTE-B15 trial page · All physician posts on KEYNOTE-B15 at ESMO 2026

Breast cancer

NATALEE: 6-year overall survival with adjuvant ribociclib

Ribociclib + NSAI vs NSAI alone in stage II–III HR+/HER2− early breast cancer. 6-year OS 91.86% vs 89.73% (difference 2.1%); HR 0.809 (95% CI 0.661–0.989); nominal one-sided P=.019. Breast cancer–specific survival HR 0.706 (0.559–0.890). 6-year iDFS 83.23% vs 77.92%, HR 0.741 (0.646–0.849). (ESMO 2026 LBA25 abstract, Dennis Slamon; data cutoff May 15, 2026; median OS follow-up 66.5 months) Adjuvant ribociclib has been FDA approved since September 17, 2024. (KOL Pulse NATALEE page)

The debate was whether a 2.1-point OS difference with a nominal P value should change practice, and how much post-progression CDK4/6 inhibitor use in the control arm matters.

“Only 2%”?

Yakup Ergün @dr_yakupergun

medical oncologist · Oct 23

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.

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Timothée Olivier, MD @Timothee_MD

oncologist, Geneva · Oct 23

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.

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Sara Tolaney @stolaney1

chief of breast oncology, Dana-Farber · Oct 23

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

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NATALEE trial page · All physician posts on NATALEE at ESMO 2026

PANKU-Breast01: iza-bren vs chemotherapy in pretreated HR+/HER2− disease

Phase 3, N=383, conducted in China: iza-bren (izalontamab brengitecan, an EGFR×HER3 bispecific ADC) vs physician’s-choice chemotherapy. PFS by BICR 8.18 vs 4.01 months, HR 0.41 (95% CI 0.33–0.53), P<0.0001. ORR 40.5% vs 20.2%. OS immature. ILD in 2 patients (1.1%), grade 1–2. (ESMO 2026 LBA50 abstract, Bo Lan; data cutoff Jul 21, 2026) Grade ≥3 TRAEs 85.3% vs 65.8%; dose reductions 64.7% vs 28.5%; grade ≥3 neutropenia 53.7%, anemia 49.5%, thrombocytopenia 46.3% with iza-bren. (LBA50 slides) Iza-bren is investigational and not FDA approved in any indication.

Physicians noted the PFS and response gains. The questions were hematologic toxicity and what comes next in sequencing.

PANKU-Breast01 trial page · All physician posts on PANKU-Breast01 at ESMO 2026

TALENT: neoadjuvant T-DXd in HR+/HER2-low early breast cancer

Phase 2, 132 patients, three arms: T-DXd alone, T-DXd + anastrozole, or T-DXd followed by docetaxel-cyclophosphamide. pCR (RCB0) 7% (3/45), 3% (1/29) and 9% (5/58). RCB0/1 16%, 17% and 17%. Grade ≥3 treatment-related AEs 24%, 17% and 28%; 3 cases of grade 2 ILD; 1 treatment-related death in the T-DXd-alone arm. (ESMO 2026 LBA23 slides, Sara A. Hurvitz) Neoadjuvant T-DXd is investigational. Enhertu is FDA approved in HER2-low breast cancer only for unresectable or metastatic disease. (KOL Pulse TALENT page)

Physicians called the pCR rates low. One noted that pCR is a limited surrogate endpoint in HR+ disease.

TALENT trial page · All physician posts on TALENT at ESMO 2026

GI cancers

SANO: active surveillance vs esophagectomy after clinical complete response

Phase 3 stepped-wedge, cluster-randomized trial, N=309, after neoadjuvant chemoradiotherapy. 5-year OS 50% with active surveillance vs 54% with surgery, HR 1.17 (95% CI 0.77–1.77), not significantly different; the confidence interval is wide and equivalence was not formally shown. DFS HR 1.39 (0.94–2.06). 5-year distant metastases 46% vs 29%, P<.01. 85 of 198 patients (43%) under surveillance were spared esophagectomy; the slide labels this figure hypothetical. (ESMO 2026 LBA78 abstract and slides; median follow-up 76 months) SANO tests a treatment strategy, not a drug.

Physicians focused on the distant-metastasis signal, the wide confidence intervals and the 41.4 Gy preoperative radiation dose.

SANO trial page · All physician posts on SANO at ESMO 2026

What to watch, Days 3–5

• Regulatory next steps: VOLGA’s durvalumab + EV is under FDA Priority Review. Amgen will engage regulators with the DeLLphi-305 interim data. Merck and Moderna plan to engage regulators on filings for intismeran.
• Follow-up data: INTerpath-001 OS is immature. PANKU-Breast01 OS is immature.
• Physician discussion on DASL-HiCaP, FOURLIGHT-1 and KEYNOTE-B49, and new readouts through October 27, on the ESMO 2026 trials page.

FAQ

Which ESMO 2026 trials did physicians discuss most on Days 1-2?

By physician posts on X on October 23-24, the most-discussed trials included DeLLphi-305, INTerpath-001, VOLGA, KEYNOTE-866, NATALEE, ENERGIZE, KEYNOTE-B15, PANKU-Breast01, TALENT and SANO.

What did DeLLphi-305 show?

Adding tarlatamab to durvalumab as first-line maintenance in extensive-stage small cell lung cancer improved median OS from 12.7 to 21.1 months (HR 0.42, 95% CI 0.32-0.54) at a prespecified interim analysis (ESMO 2026 LBA3). The first-line combination is investigational; tarlatamab is FDA approved after platinum chemotherapy.

Is the INTerpath-001 vaccine approved?

No. Intismeran autogene is investigational. INTerpath-001 showed RFS HR 0.58 (95% CI 0.45-0.75) with adjuvant pembrolizumab; OS is immature (HR 0.77, P=0.33).

Why were KEYNOTE-866 and ENERGIZE negative?

Both added a PD-1 inhibitor to neoadjuvant gemcitabine-cisplatin and missed EFS (HR 0.88 and 0.94) despite higher pCR. Physicians on X pointed to control-arm outcomes, patient selection and biology. These are cross-trial observations, not head-to-head results.

Does NATALEE show an overall survival benefit?

At 6 years, OS was 91.86% vs 89.73% (HR 0.809, 95% CI 0.661-0.989) with a nominal one-sided P=.019. Physicians disagreed on how much weight to give it. Adjuvant ribociclib has been FDA approved since September 17, 2024.