Physician reactions to KEYNOTE-866
Posts by physicians about KEYNOTE-866 during ESMO 2026 week (October 17–24, 2026), including the posts previously listed as Top Tweets. Each post is shown in full and verbatim, newest first, and linked to the original on X.
𝕏So no one knows why Durvalumab worked and Pembrolizumab and Nivo failed in perioperative MIBC trials. @DrChoueiri @tompowles1 @HHammersMD @montypal @OncoAlert @myESMO #esmo26 https://t.co/3kilxJWJnB https://t.co/xf4MDnwcxJ
𝕏Nice 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
𝕏Overall 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
𝕏🚨⭐🟠 #ESMO26 | GU Oncology — Invited Discussion KEYNOTE-866 • ENERGIZE • TROPHY-U-01 🎤 Prof. Robert Jones 🇬🇧 @OncoAlert @urologysummit 🔬 Why do apparently similar trials produce different outcomes? An excellent critical appraisal of perioperative immunotherapy in #MIBC and emerging triplet strategies in metastatic #UrothelialCancer. 📊 1️⃣ PERIOPERATIVE IMMUNOTHERAPY ✅ NIAGARA: EFS HR 0.68 ❌ KEYNOTE-866: EFS HR 0.88 ❌ ENERGIZE: EFS HR 0.94 But are these trials directly comparable? 📌 Important baseline differences: • T2 disease: 40% vs 15% vs 76% • 24-month control-arm EFS: 59.8% vs 70% vs 71.6% Different populations, endpoints and statistical designs complicate cross-trial interpretation. 🧬 2️⃣ ctDNA: PROGNOSTIC ≠ PREDICTIVE Pretreatment ctDNA positivity was associated with shorter EFS and OS. ⚠️ In ENERGIZE, baseline ctDNA positivity differed between arms (59% vs 51%), potentially introducing prognostic imbalance. 🔬 ctDNA clearance before cystectomy identified patients with more favorable outcomes. But can ctDNA clearance identify candidates for bladder preservation? Not yet! Prospective validation is essential before considering omission of radical cystectomy. 💊 3️⃣ DUAL ADC + IMMUNOTHERAPY: THE NEXT FRONTIER? TROPHY-U-01 Cohort 7: ✅ ORR 81% ✅ Median PFS 19.3 months ✅ Median DoR 16.7 months ⚠️ Grade ≥3 treatment-related AEs: 52% ⚠️ Treatment-related discontinuation of ≥1 agent: 33% Promising efficacy, but only 21 patients and no randomized comparator. ⭐ MY POINT OF VIEW CLINICAL PEARLS 🔹 A positive trial does not prove the superiority of one checkpoint inhibitor over another. 🔹 ctDNA may redefine risk stratification, but molecular clearance is not yet a license to omit surgery. 🔹 Dual ADC intensification is scientifically exciting, but added efficacy must justify added toxicity. 💡 The future of GU oncology is not about treating everyone more aggressively. It is about treating the right patient with the right strategy, at the right time. 📌 PRACTICE IMPLICATION These new results do not independently establish a new standard of care. Individual trials must be interpreted on their own merits. Access also matters: perioperative gemcitabine/cisplatin + durvalumab remains an important option where EV + pembrolizumab is unavailable. 🌍 GU Oncology Community @gbanna74 @ravikanesvaran @urologysummit @tompowles1 @PGrivasMDPhD @apolo_andrea @sonpavde @DrYukselUrun @yekeduz_emre @drenriquegrande @TiansterZhang @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #GUOncology #ctDNA #OncoAlert
𝕏🚨 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.
𝕏6. KEYNOTE-866: PeriOp pembro + neoadj cis/gem vs placebo + chemo in cisplatin-eligible MIBC. - EFS: median 74.1 mo vs NR (HR 0.88; p=0.14) - No significant EFS or OS benefit - EV+pembro (or perhaps Durva-EV will be) preferred SOC. 7/8 https://t.co/hTQ3qFh0F1 https://t.co/RcyWrrRaEh
𝕏#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
𝕏ENERGIZE: perioperative CisGem +/- Nivo in MIBC. No improvement in survival endpoints, just like KN-866. Food for thought… #ESMO26 https://t.co/WvI1UDVNMD
𝕏Durvalumab plus cisplatin showed positive results, while the pembrolizumab and nivolumab trials were negative. I’m not sure how to make sense of this puzzle. #ESMO2026 @tompowles1 @ProfSyedHussain @PGrivasMDPhD @PGrivasMDPhD @montypal @DrYukselUrun https://t.co/7AXG6J6zOj
𝕏🚨 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
𝕏🎯 Starting the GU oral session! #ESMO26 @JensBedke presenting 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/nOgomCyPnE
𝕏It hard to explain why 1 trial with gem/cis +/-PD(L)1 (NIAGARA) is +ve for EFS/OS and 2 very similar trials (presented today) are negative in MIBC. Potentially NIAGARA has the highest risk population, not all respond to IO and the maintenance phase the most effect- but the OS of gem/cis pembro HR of 1 is concerning. This reflects what we saw in metastatic disease with contradictory results for the big combination trials. Overall EVP looks better and more consistent #ESMO26 @myESMO @Annals_Oncology @OncoAlert
𝕏Negative 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
𝕏Full 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
𝕏🚨⭐ #ESMO26 |Abstract 4735O KEYNOTE-866 🟠 Perioperative pembrolizumab or placebo + neoadjuvant cisplatin and gemcitabine in muscle-invasive bladder cancer: Phase III KEYNOTE-866 🎤 Presented by Jens Bedke 🇩🇪 @OncoAlert 🔬 Can adding perioperative pembrolizumab to cisplatin-based neoadjuvant chemotherapy improve outcomes in cisplatin-eligible MIBC? 📊 STUDY DESIGN Phase III, randomized, double-blind, placebo-controlled trial. 👥 N=907 patients with cisplatin-eligible MIBC. 🔹 Pembrolizumab + gemcitabine/cisplatin → radical cystectomy → adjuvant pembrolizumab (n=453) 🔹 Placebo + gemcitabine/cisplatin → radical cystectomy → adjuvant placebo (n=454) Median follow-up: 60.9 months. 📊 KEY RESULTS ❌ Event-free survival (PRIMARY ENDPOINT) • Median EFS: 74.1 months vs NR • HR 0.88 (95% CI 0.71–1.10) • p=0.1366 ➡️ No statistically significant EFS improvement. 📈 Pathological complete response (pCR) ✅ 44.4% vs 35.8% • Estimated difference: +8.9 percentage points (95% CI 2.5–15.1). ⚠️ Higher pCR did NOT translate into a statistically significant improvement in the primary EFS endpoint. 📊 Overall survival • Median OS: NR in both arms • HR 1.00 (95% CI 0.79–1.27) ➡️ No observed OS advantage. pCR and OS were not formally tested for statistical significance under the hierarchical testing strategy. 🏥 Surgery • Underwent cystectomy: 91.6% vs 87.9%. ⚠️ SAFETY • Grade 3–5 treatment-emergent AEs: 80.2% vs 75.1%. • Grade 3–5 immune-mediated AEs/infusion reactions: 8.9% vs 1.8%. 🔬 CONCLUSION KEYNOTE-866 did not meet its primary EFS endpoint. Despite increased pCR rates, perioperative pembrolizumab added to neoadjuvant cisplatin/gemcitabine did not demonstrate a significant EFS benefit. ⭐ MY POINT OF VIEW | CLINICAL PEARL A higher pathological response rate is encouraging, but it is not enough to redefine a standard of care. In curative-intent MIBC, durable disease control and survival must drive treatment decisions. 📌 These findings do not support routinely adding perioperative pembrolizumab to neoadjuvant gemcitabine/cisplatin in cisplatin-eligible MIBC. 💡 More treatment does not necessarily mean better outcomes. The real challenge is identifying which patients benefit from intensification—and which do not. 🌍 GU Oncology Community @urologysummit @gbanna74 @ravikanesvaran @PGrivasMDPhD @tompowles1 @apolo_andrea @sonpavde @montypal @DrChoueiri @neerajaiims @HHammersMD @TiansterZhang @drenriquegrande @crisbergerot @DrDanielHeng @Silke_Gillessen @EfstathiouEleni @BraunMDPhD @brian_rini @AOmlin @DrYukselUrun @yekeduz_emre @cdanicas @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #MIBC #GUOncology #ClinicalTrials #OncoAlertAF
𝕏Excellent 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
𝕏KEYNOTE-866 did not show EFS not OS. Great presentation 👏🏼by Prof Jens Bedke #ESMO26 @OncoAlert @Uromigos @urotoday @Uroweb @DGUrologie @high5md https://t.co/h2WiciZeJF
𝕏🚨⭐🟠 #ESMO26 GU Oncology Invited Discussion 🎤 Prof. Robert Jones 🇬🇧 @OncoAlert 🔬 Why did NIAGARA succeed while KEYNOTE-866 and ENERGIZE failed to meet their primary efficacy endpoints? 📊 EFS HR: ✅ NIAGARA: 0.68 ❌ KEYNOTE-866: 0.88 ❌ ENERGIZE: 0.94 🧩 Different populations, baseline risks, eligibility criteria and trial designs complicate comparisons. ⭐ MY POINT OF VIEW Different outcomes across trials do not establish superiority of PD-L1 over PD-1 blockade. 💡 In curative-intent MIBC, patient selection, endpoint definitions and absolute clinical benefit matter as much as the HR. Cross-trial comparisons generate hypotheses, not definitive conclusions. 🌍 GU Oncology Community @gbanna74 @ravikanesvaran @urologysummit @tompowles1 @PGrivasMDPhD @apolo_andrea @sonpavde @AndreaNecchi @drenriquegrande @DrYukselUrun @yekeduz_emre @cdanicas @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #UrothelialCancer #GUOncology #ADC #ClinicalTrials
𝕏🚨 A negative phase III trial can still sharpen the field. @OncoAlert At #ESMO26, KEYNOTE-866 tested whether adding perioperative pembrolizumab to neoadjuvant gemcitabine/cisplatin and radical cystectomy could improve outcomes in cisplatin-eligible MIBC. 📊 n=907 ➡️ EFS: 74.1 mo vs NR HR 0.88 (0.71–1.10), p=.1366 ➡️ pCR: 44.4% vs 35.8% ➡️ OS: HR 1.00 (0.79–1.27) ⚠️ Grade 3–5 TEAEs: 80.2% vs 75.1% The key point: perioperative pembrolizumab did not significantly improve EFS. 🎯 Why this matters: not every perioperative IO strategy adds meaningful benefit to cisplatin-based chemotherapy. For me, this is a reminder that the perioperative MIBC space cannot be treated as one interchangeable class effect. We need to understand: 🔹 which combinations truly improve long-term outcomes 🔹 whether pCR gains translate into survival benefit 🔹 which patients need intensification 🔹 and how biomarkers may help us avoid adding toxicity without enough efficacy More therapy is not automatically better perioperative therapy. Better selection matters. Important data from @garysteinbergmd @DrChrisHoimes and the KEYNOTE-866 investigators. Pinging @DrChoueiri @tompowles1 @apolo_andrea @PGrivasMDPhD @AndreaNecchi @DrYukselUrun @drenriquegrande @crisbergerot @niklas_kluemper @nataliagandur #OncoAlert #ESMO26 #BladderCancer #MIBC #Immunotherapy #PerioperativeTherapy #GUOncology
𝕏Does adding periop pembrolizumab to neoadjuvant gemcitabine–cisplatin, followed by radical cystectomy and adjuvant pembrolizumab, improve outcomes in cisplatin-eligible muscle-invasive bladder cancer (MIBC)? KEYNOTE-866 trial @ ESMO 2026 N=907 Median FU 5y EFS HR 0.88 p=0.13 https://t.co/YaVmGMbn0z
𝕏🚨 New ESMO 2026 data challenge our understanding of perioperative therapy in MIBC! KEYNOTE-866 (phase III, n=707), ENERGIZE (phase III, n=653): Adding perioperative pembro or nivolumab to neoadjuvant gemcitabine/cisplatin did not significantly improve EFS and OS, despite numerically higher pCR! Yet NIAGARA demonstrated significant EFS (HR 0.68) and OS (HR 0.75) benefits with perioperative durvalumab. Why does one chemoimmunotherapy strategy succeed while others fails? Different patient populations, trial designs, or underlying biology? We urgently need predictive biomarkers—not just another checkpoint inhibitor. Meanwhile, new KEYNOTE-905 data in cisplatin-ineligible MIBC (ad hoc, n=255) show: • Pembrolizumab alone: pCR 25.3%; EFS HR 0.71 vs surgery alone. • EV+pembrolizumab: pCR 58.8%; EFS HR 0.40 vs surgery alone. The key question is no longer simply whether to add immunotherapy—but which patients need chemotherapy, ADC-based therapy, or both. Histology, NECTIN4/HER2 biology, and longitudinal ctDNA deserve prospective evaluation as treatment-selection tools. Exciting times for MIBC—but precision must catch up with therapeutic progress. @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
𝕏More pCR didn’t translate into EFS or OS. KEYNOTE-866: an important negative phase 3 in cisplatin-eligible MIBC. #ESMO26 #BladderCancer https://t.co/Ctmh4fcbF5
KEYNOTE-866 Key Takeaways
KOL Pulse analysisENERGIZE and KEYNOTE-866: Two Negative Phase 3 Trials in MIBC, and the NIAGARA Question →Both trials side by side, the presented slides, and the full physician debate.Event-free survival (primary)
EFS events 157 (34.7%) vs 168 (37.0%). Median EFS 74.1 months (95% CI 72.4–NR) with pembrolizumab vs not reached (67.7–NR) with placebo. HR 0.88 (95% CI 0.71–1.10), one-sided P=0.1366; not statistically significant against a one-sided boundary of 0.0225. 24-month EFS 76.7% vs 70.0%; 60-month EFS 63.5% vs 61.9%. (ESMO 2026 4735O, Bedke; data cutoff 26-Jan-2026)
EFS HR 0.88 · P=0.1366 · not metSource: Bedke et al., Annals of Oncology (DOI 10.1016/j.annonc.2026.10.106) ↗
Overall survival and pCR (key secondary)
OS events 135 (29.8%) vs 135 (29.7%); median not reached in either arm; HR 1.00 (95% CI 0.79–1.27); 60-month OS 70.8% vs 70.9%. pCR by central pathology review 44.4% (200/450; 95% CI 39.8–49.2) vs 35.8% (162/453; 95% CI 31.3–40.4); estimated difference 8.9% (95% CI 2.5–15.1). Neither OS nor pCR was formally tested for statistical significance under the statistical design. (ESMO 2026 4735O, Bedke; data cutoff 26-Jan-2026)
OS HR 1.00 · pCR 44.4% vs 35.8%Source: ClinicalTrials.gov NCT03924856 · presented slides (KOL capture) ↗
Survival and response, KEYNOTE-866 (ESMO 2026 4735O, Bedke; data cutoff 26-Jan-2026)
| Measure | Pembro + cis/gem (n=453) | Placebo + cis/gem (n=454) |
|---|---|---|
| EFS events | 157 (34.7%) | 168 (37.0%) |
| Median EFS | 74.1 mo (72.4–NR) | Not reached (67.7–NR) |
| 24-month EFS | 76.7% | 70.0% |
| 36-month EFS | 69.2% | 66.3% |
| 48-month EFS | 66.0% | 62.3% |
| 60-month EFS | 63.5% | 61.9% |
| OS events | 135 (29.8%) | 135 (29.7%) |
| Median OS | Not reached | Not reached |
| 24-month OS | 82.8% | 81.7% |
| 36-month OS | 76.8% | 76.6% |
| 48-month OS | 72.9% | 73.4% |
| 60-month OS | 70.8% | 70.9% |
| pCR (central review) | 44.4% (200/450) | 35.8% (162/453) |
EFS HR 0.88 (95% CI 0.71–1.10), one-sided P=0.1366, not significant (one-sided boundary 0.0225). OS HR 1.00 (95% CI 0.79–1.27), not formally tested. pCR estimated difference 8.9% (95% CI 2.5–15.1), not formally tested. Landmark values as labeled on the presented Kaplan-Meier slides.
Safety
Immune-mediated AEs and infusion reactions occurred in 130 (28.9%) vs 42 (9.4%) patients; grade 3–5 in 40 (8.9%) vs 8 (1.8%); serious in 31 (6.9%) vs 8 (1.8%); none led to death with pembrolizumab vs 1 (0.2%) with placebo. Hypothyroidism (10.4%) was the most frequent immune-mediated AE with pembrolizumab. Any subsequent therapy 18.8% vs 23.8%. The presenters reported a manageable safety profile with no new safety signals. (ESMO 2026 4735O, Bedke; data cutoff 26-Jan-2026)
Grade 3–5 immune-mediated AEs 8.9% vs 1.8%Source: presented safety slide (posted by @nataliagandur) ↗
Regulatory status
⚠️ Perioperative pembrolizumab plus neoadjuvant gemcitabine-cisplatin is not approved for MIBC; the presented conclusion states it is not supported. ✅ Perioperative enfortumab vedotin plus pembrolizumab is FDA-approved for MIBC: November 21, 2025 for cisplatin-ineligible patients (KEYNOTE-905) and July 10, 2026 for cystectomy candidates regardless of cisplatin eligibility (KEYNOTE-B15). (FDA)
KOL pulse
Physicians posting from the session called the trial negative, noted that the higher pCR rate did not translate into EFS or OS, and asked why NIAGARA was positive. Several noted the strong outcomes in the placebo arm.
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Top KOLs Discussing KEYNOTE-866
KEYNOTE-866 Key Slides & Visuals
ESMO 2026 slides
KEYNOTE-866 Trial Design
KEYNOTE-866 asked whether perioperative pembrolizumab improves outcomes when added to neoadjuvant cisplatin-gemcitabine and radical cystectomy in cisplatin-eligible MIBC. It is described by the investigators as the first placebo-controlled trial of perioperative PD-1/PD-L1 immunotherapy with neoadjuvant cisplatin-gemcitabine. Most patients had cT3/cT4aN0 disease at baseline (84.5% vs 84.8%); 14.8% vs 14.5% had cT2N0 disease.
Jens Bedke presented the final EFS analysis at ESMO 2026 (Abstract 4735O), with a concurrent paper in Annals of Oncology. The presented conclusions state that efficacy in the placebo arm surpassed conventional benchmarks for neoadjuvant cisplatin-gemcitabine and that perioperative enfortumab vedotin plus pembrolizumab has become a standard of care in MIBC.
Study Design
Phase III, randomized 1:1, double-blind, placebo-controlled. (Study design slide; ClinicalTrials.gov NCT03924856)
Population
Cisplatin-eligible MIBC; ITT 453 vs 454. Baseline cT2N0 14.8% vs 14.5%, cT3/cT4aN0 84.5% vs 84.8%, cT1–4aN1 0.7% vs 0.7%; PD-L1 CPS ≥10 56.7% vs 56.2%. (Baseline slide)
Interventions
Pembrolizumab 200 mg or placebo Q3W + cisplatin 70 mg/m² + gemcitabine 1000 mg/m² x4 → RC + PLND → pembrolizumab or placebo Q3W x13 (4 neoadjuvant cycles; 13 adjuvant cycles).
Endpoints
Primary: EFS by investigator assessment. Key secondary: OS; pCR (pT0N0) by central pathology review. Other: safety.
Presenter
Jens Bedke — ESMO 2026 Proffered paper session, Genitourinary tumours, renal and urothelial, October 23, 2026, Abstract 4735O. Concurrent publication: Annals of Oncology (DOI 10.1016/j.annonc.2026.10.106).
Sponsor
Merck Sharp & Dohme LLC (ClinicalTrials.gov).
Design sources: ESMO 2026 4735O, Bedke; data cutoff 26-Jan-2026.
KEYNOTE-866 in the News
KEYNOTE-866 FAQ
What is the KEYNOTE-866 trial?
KEYNOTE-866 (NCT03924856) is a Merck double-blind phase III trial in cisplatin-eligible muscle-invasive bladder cancer comparing perioperative pembrolizumab with placebo, each with neoadjuvant cisplatin-gemcitabine and radical cystectomy. See Trial Design.
What did KEYNOTE-866 show at ESMO 2026?
The primary endpoint, event-free survival, was not met (HR 0.88, one-sided P=0.1366). Overall survival and pCR were not formally tested. All figures with the data cut-off are in At a Glance.
Is pembrolizumab with gemcitabine-cisplatin approved for MIBC?
No. Perioperative pembrolizumab with neoadjuvant gemcitabine-cisplatin is not approved for MIBC. Perioperative enfortumab vedotin plus pembrolizumab is FDA-approved for MIBC, based on KEYNOTE-905 and KEYNOTE-B15. See At a Glance.
Why was NIAGARA positive when KEYNOTE-866 was negative?
The reason is not established. Physicians and the invited discussant pointed to differences in disease stage at entry, control-arm outcomes, endpoint definitions and trial design. NIAGARA (durvalumab) improved EFS (HR 0.68) and OS (HR 0.75); these are cross-trial observations, not a head-to-head comparison.
What were the safety findings?
Immune-mediated adverse events and infusion reactions were more frequent with pembrolizumab than placebo; the investigators reported a manageable safety profile with no new safety signals. Rates: At a Glance.
Key KOL Sentiments - KEYNOTE-866
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 26, 2026. Statistics carry their source and data-cut label in place; every quote is verbatim from the physician’s own post.