October 23–27, 2026 · Madrid · 3132 items
23 people · 26 posts · 1 abstract
Heat now 2·Peak in the comparable set 3 (Oct 24 09:00)·Change over 24h in the comparable set –·Participants now 4
In muscle-invasive bladder cancer (MIBC), recurrence rates remain high and prognosis poor even with aggressive treatment such as radical cystectomy; in cisplatin-eligible patients, neoadjuvant chemotherapy improves outcomes, but the overall survival gain is modest [1]. Based on this unmet need and on efficacy signals from Phase Ib/II studies of pembrolizumab monotherapy or combination as neoadjuvant therapy [1], the randomized, double-blind Phase III KEYNOTE-866 was launched to test perioperative pembrolizumab or placebo plus chemotherapy, alongside KEYNOTE-905/EV-303 for cisplatin-ineligible patients [1]. The immune-related adverse event profile of immune checkpoint inhibitors—including the relatively common endocrine toxicities—has also been systematically described [5].
What was reported at ESMO26 is the primary result of KEYNOTE-866 (Abstract 4735O, presented by Jens Bedke). The study enrolled 907 cisplatin-eligible MIBC patients randomized to pembrolizumab + gemcitabine/cisplatin → radical cystectomy → adjuvant pembrolizumab (n=453), or the corresponding placebo regimen (n=454), with a median follow-up of 60.9 months. The primary endpoint of EFS was not met: median EFS 74.1 months vs NR, HR 0.88 (95% CI 0.71–1.10), p=0.1366; pCR was 44.4% vs 35.8%, with an estimated difference of +8.9 percentage points (95% CI 2.5–15.1), but the higher pCR did not translate into an EFS benefit; OS HR 1.00 (95% CI 0.79–1.27), with median OS NR in both arms, and neither pCR nor OS was formally tested under the hierarchical testing strategy. Cystectomy was performed in 91.6% vs 87.9%; Grade 3–5 treatment-emergent AEs were 80.2% vs 75.1%, and Grade 3–5 immune-mediated AEs/infusion reactions 8.9% vs 1.8%.
Relative to prior knowledge, this readout put the Phase I/II signals [1] to the Phase III test and returned a negative answer: adding perioperative pembrolizumab on top of chemotherapy raised pCR but delivered no EFS benefit, and the on-site conclusion does not support routinely adding this strategy in cisplatin-eligible MIBC. The invited discussion (Robert Jones) also placed the trial alongside NIAGARA (EFS HR 0.68) and ENERGIZE (EFS HR 0.94), noting marked baseline differences in T2 disease (40% vs 15% vs 76%) and 24-month control-arm EFS (59.8% vs 70% vs 71.6%), so cross-trial interpretation demands caution; the discussion also touched on ctDNA (pretreatment positivity associated with shorter EFS/OS, preoperative clearance with better outcomes, but not yet sufficient to omit cystectomy) and the dual ADC + immunotherapy data from TROPHY-U-01 Cohort 7 (ORR 81%, median PFS 19.3 months)—a separate thread that does not change the negative conclusion of KEYNOTE-866 itself.
Limitations are that OS and pCR were not formally tested statistically, the cross-trial comparisons are exploratory, and pCR pathology assessment is not standardized across trials; immune checkpoint inhibitors benefit only a subset of patients, with responses related to features such as tumor immune phenotype [3], so which patients truly need intensification awaits prospective validation, and these results alone do not independently change the current treatment landscape.
Perioperative pembrolizumab (pembro) or placebo (pbo) + neoadjuvant cisplatin (cis) and gemcitabine (gem) in participants (pts) with muscle-invasive bladder cancer (MIBC): the double-blind, phase 3 KEYNOTE-866 study
https://esmocongress.esmo.org🚨⭐ #ESMO26 |Abstract 4735O KEYNOTE-866 🟠
🚨⭐🟠 #ESMO26 | GU Oncology — Invited Discussion
Infographic to show the cross trial comparisons of 3 phase III perioperative IO trials in MIBC Only one is positive. Why ? I don't know. Looking forward towards full data of 2 negative trials on day 1 #esmo26 @myESMO
OncoAlert 4Sight Abstracts to be Presented at #ESMO26
🚨 #ESMO26 | KEYNOTE-866: A disappointing result in MIBC!
🔎 New phase III MIBC data at #ESMO26:
A positive trial is not a class effect.
#ESMO26: No significant increase in event-free survival seen with peri-operative pembrolizumab or nivolumab in the KEYNOTE-866 or ENERGIZE #ClinicalTrials of resectable muscle-invasive #BladderCancer (#MIBC), as discussed by @y_loriot 🔗 https://ow.ly/TbzF50ZZ0s2 #InsightsbyESMO
🚨 A negative phase III trial can still sharpen the field.
OncoAlert 4Sight Abstracts to be Presented at #ESMO26 Perioperative Pembrolizumab or Placebo + Neoadjuvant Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer: The Double-Blind, Phase 3 KEYNOTE-866 Study @garysteinbergmd @DrChrisHoimes 🔬 Phase 3, double-blind (n=907): perioperative pembrolizumab or placebo + neoadjuvant gemcitabine-cisplatin and RC + PLND in cisplatin-eligible MIBC. Primary endpoint: EFS. ➡️ Median 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); neither formally tested ➡️ Grade 3–5 TEAEs 80.2% vs 75.1% ✅ Perioperative pembrolizumab did not confer a statistically significant EFS benefit; safety profile manageable and consistent with prior reports. #BladderCancer 🎙️ Jens Bedke 👥 Arlene Siefker-Radtke · Gary Steinberg · Hiroyuki Nishiyama · Xiao Fang · Ritesh Kataria · Blanca Homet Moreno · Christopher Hoimes (4Sight Made from Abstracts publicly available at the ESMO website) Pinging Our 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, @niklas_kluemper
#ESMO26 Day 1 has arrived! Follow along with @OncoAlert for full coverage!
The OncoAlert #ESMO26 PULSE Faculty is ready! 🇪🇸 WE ARE HERE! Meet our incredible faculty reporting live from Madrid: @cdanicas @hoperugo @DrChoueiri @TiansterZhang @matteolambe @NiuSanford @stolaney1 @christine_lovly @amerseburger @GlopesMd @tompowles1 @montypal @Icro_Meattini @PGrivasMDPhD @brian_rini @CathyEngMD @apolo_andrea @AndreaNecchi @DrSGraff @BenWestphalen @graokane @to_be_elizabeth @ElisaAgostinett @nataliagandur @UOzkerim @DrMirallas @DrYukselUrun @Lucarecco @mzugman @HHorinouchi @p_ciracimd @DraMartinezLago @DrVilmaPBarcia @GIMedOnc @MarioBalsaMD @scocmem @AmandaNizamMD @GaiaGriguolo @JankovicK @Dr_Oncologista @Erman_Akkus @WeOncologists @niklas_kluemper @Markuseckstein3 Whether you're at #ESMO26 in Madrid or following from home, our faculty will bring you the latest science, insights, and key updates straight from the congress. OncoAlert has you covered! Less noise. No nonsense. Just science. Strictly by colleagues, for colleagues!
🚨⭐ #ESMO26 | GU ONCOLOGY — DAY 1 HIGHLIGHTS
KEYNOTE-866: Negative for EFS.
🚨 Negative results from KEYNOTE-866 at #ESMO26.
🚨⭐ #ESMO26 | GU ONCOLOGY — DAY 1 HIGHLIGHTS
🚨⭐ #ESMO26 | GU ONCOLOGY — DAY 1 HIGHLIGHTS @OncoAlert 🟠🔵 From perioperative immunotherapy to molecular precision and next-generation treatments. A remarkable opening day in GU oncology, with important lessons for both #BladderCancer and #ProstateCancer. Here are our key scientific takeaways 👇 🟠 1️⃣ KEYNOTE-866 Abstract 4735O ❌ Perioperative pembrolizumab + gemcitabine/cisplatin failed to 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% 💡 Higher pathological response did not translate into a statistically significant EFS benefit. 🟠 2️⃣ ENERGIZE Abstract 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% 🔬 These findings reinforce the need to interpret response endpoints alongside durable clinical outcomes. 🟠 3️⃣ KEYNOTE-905 & KEYNOTE-B15 | 4733O / 4734O ✅ The exploratory three-arm KEYNOTE-905 analysis favored EV + pembrolizumab over surgery alone. 📊 OS HR 0.48 pCR: 58.8% vs 25.3% with pembrolizumab alone and 10.3% with surgery alone. 🧬 KEYNOTE-B15: ctDNA clearance with EV + pembrolizumab vs gemcitabine/cisplatin: ✅ 82.1% vs 66.7% ctDNA positivity was associated with poorer EFS. 📌 Molecular monitoring offers exciting opportunities for risk stratification, but ctDNA-guided treatment decisions still require prospective validation. 🟠 4️⃣ TROPHY-U-01 COHORT 7 4742O 💊 SG + EV + zimberelimab in untreated metastatic urothelial cancer. ✅ ORR: 81% ✅ Median PFS: 19.3 months ✅ Median DoR: 16.7 months ⚠️ Phase Ib, only 21 patients, with substantial toxicity. Promising—but not yet practice-changing. 🔵 5️⃣ CAPItello-281 LBA56 Updated overall survival in PTEN-deficient de novo mHSPC. 📊 Capivasertib + abiraterone vs placebo + abiraterone: ✅ Median OS: 57.4 vs 46.5 months HR 0.82 (95% CI 0.68–0.99) ⚠️ The prespecified statistical significance threshold was not met. An encouraging survival signal, but not a formally established OS benefit. 🔵 6️⃣ THE NEXT FRONTIER IN PROSTATE CANCER Today's educational sessions highlighted major advances in: ☢️ PSMA-targeted radioligand therapy 🧬 AR degraders and RIPTACs 💊 Next-generation ADCs 🔬 T-cell engagers and precision immunotherapy The key challenge is moving from promising biological activity toward durable clinical benefit, acceptable toxicity and better patient selection. ⭐ POINT OF VIEW More treatment does not always mean better outcomes. And an impressive response rate does not automatically establish a new standard of care. Today's data reinforce three essential principles: ✅ Robust survival endpoints matter. ✅ Biomarkers must move from prognostic value to validated therapeutic guidance. ✅ Novel combinations require careful assessment of efficacy, toxicity and clinical applicability. 💡 The future of GU oncology is not simply treatment intensification—it is smarter, biologically informed treatment selection. 🎯 The right strategy. The right patient. The right time. Outstanding scientific discussions throughout Day 1! @gbanna74 @ravikanesvaran @nataliagandur @neerajaiims @Sebastiano_Buti @CinziaConted @dralishadamani @amg120395 @PGrivasMDPhD @koshkin85 @MicheleMaffezz @ParamMariappan @dmukherji @VanitaNoronha @montypa @DanieleRaggi83 @PasRescigno @jteoh_hk @alison_tree @DrYukselUrun @yekeduz_emre @AgrawalTrush @ONCOassist @VuMedi @ProstateUK @OncologyNT @OncJournal #GUOncology #BladderCancer #ProstateCancer #mCRPC #MIBC #PrecisionOncology
#ScienceLink #Madrid2026 #ESMO26 #KEYNOTE866 #Pembrolizumab