Physician reactions to KEYNOTE-905
Posts by physicians about KEYNOTE-905, newest first: ESMO 2026 week (October 17–24, 2026), then earlier posts back to the August 2025 topline announcement, including the ESMO 2025 readout, the FDA approval and the NEJM publication. Each post is shown in full and verbatim and linked to the original on X.
𝕏💔 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
𝕏KEYNOTE-905 vs VOLGA | EV has two partners in MIBC! Both perioperative strategies improve EFS and OS in cisplatin-ineligible MIBC. 🔹 KEYNOTE-905: EV + pembrolizumab, with postoperative EV. 🔹 VOLGA: EV + durvalumab, without postoperative EV. The key difference? Postoperative EV — 6 cycles vs NONE! ⚠️ Different trials, different designs. Cross-trial comparisons cannot establish superiority. @myESMO @OncoAlert #ESMO26 #BladderCancer #MIBC #MVOnco
𝕏🚨 VOLGA is positive! But how much perioperative EV do we really need in MIBC? Interesting comparison with KEYNOTE-905 at #ESMO26: 🔹 VOLGA (EV + durvalumab): 2-year EFS 64%, OS 78%, pCR 45%. EFS HR 0.51. 🔹 KEYNOTE-905 (EV + pembrolizumab): 2-year EFS 74.7%, OS 79.7%, pCR 57.1%. EFS HR 0.40. Numerically lower EFS and pCR in VOLGA. Why? Different patient populations and tumor characteristics? Different study designs? It seems premature to attribute these differences to pembrolizumab vs durvalumab. But the most intriguing question is how much benefit does adjuvant EV actually add? VOLGA achieved a significant OS benefit with just 3 neoadjuvant EV cycles and NO adjuvant EV, whereas KEYNOTE-905 planned 9 EV cycles (3 neoadjuvant + 6 adjuvant)—and fewer than half of patients reportedly completed the full planned EV course. Could pCR and ctDNA clearance help us safely omit adjuvant EV and reduce cumulative toxicity? ⚠️ Cross-trial comparisons are hypothesis-generating, not evidence of superiority or equivalence. Only prospective trials can establish the incremental benefit of adjuvant EV. More EV ≠ necessarily better outcomes. Let’s identify who really needs it! 🔬 @OncoAlert @weoncologists @tompowles1 @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
𝕏With 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
𝕏The KN905 MIBC trial includes a 3rd, less celebrated arm of single agent pembro. Results show pembro delivers an important contribution to the EVP. The trial is small and EVP performs better, but pCR rates for pembro of 35% are in the same range as neoadjuvant cisplatin chemo while EFS/OS HRs of 0.71/O.76 vs surgery are impressive. Pembro had about half the toxicity of EVP, underlining the relevance of therapy duration. VOLGA (3 cycles of EVD), is a half way between Pembro alone and 9 cycles of EVP. @Annals_Oncology #ESMO26 @Annals_Oncology @OncoAlert
𝕏Perioperative EV + Pembro momentum by #DrAndersUllen in KEYNOTE-905 Ph.III ad hoc analysis of cis-ineligible MIBC. 2-yr EFS: 75.8% EV/Pembro vs 55.8% Pembro vs 41.0% surgery alone. EFS HR 0.40 vs 0.71 (each vs control). pCR 58.8% vs 25.3% vs 10.3%. #ESMO26 #BladderCancer @myESMO @OncoAlert
𝕏#ESMO26 How much does each drug contribute to perioperative EV + pembrolizumab in MIBC? 🚨A 3-arm analysis of KEYNOTE-905/EV-303 (N=255). EV+P vs P alone vs surgery: 🔹 3-year EFS: 69.5% vs 49.6% vs 37.4% 🔹 pCR: 58.8% vs 25.3% vs 10.3% 🔹 Pathologic downstaging: 65.9% vs 33.7% vs 14.9% 🔹 EFS HR vs surgery: 0.40 with EV+P; 0.71 with P alone 📌The efficacy gradient suggests both EV and pembrolizumab contribute to the combination's activity, with substantially greater benefit from EV+P. 📌Important caveat: descriptive, ad hoc analysis without formal statistical testing. @UroToday @myESMO
𝕏🔬 Great summary by @niklas_kluemper on KEYNOTE-905/EV-303 at #ESMO2026. Let me add the pathology angle, because his key question is ours to answer. The ad hoc analysis, 255 concurrently randomised, cisplatin-ineligible: 📊 2-yr EFS 41% / 56% / 76% (cystectomy / pembro / EV+P) 🔬 pCR 10% / 25% / 59% 📉 EFS HR 0.71 (0.47–1.07) for pembro, 0.40 (0.25–0.65) for EV+P ⚠️ Grade ≥3 TEAEs 42% / 70% / 69% Two things I keep coming back to 🧠 1️⃣ The toxicity numbers look reassuring and are not. 70 vs 69% grade ≥3 says EV adds no extra severe events, but a single rate collapses two very different profiles. Neuropathy, skin and metabolic toxicity in a curative-intent setting are not interchangeable with immune-related events, and they persist in survivors. Equal rates, unequal consequences. 2️⃣ 41% of patients on EV+P still have residual disease. We will not find them just with a IHC cutoff. Membranous Nectin-4, read on the membrane only, together with histological subtype and divergent squamous differentiation, is the most informative combination we already have and routinely leave unmeasured. And a pathology point that follows directly: once pCR carries this much weight, ypT0N0 at cystectomy becomes a high-stakes diagnosis. Thus, Sampling protocols and regression assessment need to be standardised and centrally reviewed, not left to local practice. 🎯 Also worth stating plainly: this is an ad hoc comparison, not a powered head-to-head. Pembro alone did not separate from surgery here (CI crosses 1). Interpret the three-arm ranking accordingly. Looking forward to Sunday's symposium. 🎤 ESMO 2026 | KEYNOTE-905/EV-303 | Abstract 4733O @niklas_kluemper @OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot #Uropathology #BladderCancer #blcsm #pathtwitter
𝕏KEYNOTE-905: pembro alone raises a question worth testing. Who might safely need less? @myESMO @FAndreMD @curijoey @DrChoueiri @OncoAlert @OpenMedicineHQ #ESMO26 @Uromigos https://t.co/Qplp3Osdrc
𝕏Cisplatin-ineligible ≠ treatment-ineligible. KEYNOTE-905: 2-year EFS 75.8% with EV/pembro vs 41% with surgery alone. @myESMO @FAndreMD @curijoey @DrChoueiri @OncoAlert @OpenMedicineHQ #ESMO26 https://t.co/lWizzlUDP2
𝕏🚨⭐🟠 #ESMO26 | Abstract 4733O | KEYNOTE-905 / EV-303 Perioperative Pembrolizumab or Enfortumab Vedotin + Pembrolizumab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer: Ad Hoc Analysis 🎤 Presented by Anders Ullén 🇸🇪 @OncoAlert 🔬 What is the contribution of each agent to the benefit of perioperative EV + pembrolizumab? 📊 STUDY DESIGN Exploratory 3-arm analysis | N=255 Patients with #MIBC ineligible for or declining cisplatin, concurrently randomized to: 🟢 EV + pembrolizumab (n=85) 🔵 Pembrolizumab alone (n=83) 🔴 Radical cystectomy + PLND alone (n=87) 📊 KEY RESULTS ✅ OVERALL SURVIVAL 🔹 EV + pembro vs control: HR 0.48 (95% CI 0.29–0.80) 🔹 Pembro vs control: HR 0.76 (95% CI 0.48–1.20) 📈 Median OS: • EV + pembro: NR • Pembro: 51.0 months • Control: 41.7 months ✅ PATHOLOGICAL COMPLETE RESPONSE 🟢 EV + pembro: 58.8% 🔵 Pembro: 25.3% 🔴 Control: 10.3% Absolute differences vs control: • EV + pembro: +48.6 percentage points • Pembro: +15.7 percentage points 📌 EFS and OS favored perioperative EV + pembro versus surgery alone, while pembrolizumab monotherapy showed numerically favorable outcomes. ⚠️ SAFETY Grade ≥3 AEs: • Neoadjuvant: 44.0% vs 20.7% (EV + pembro vs pembro) • Adjuvant: 60.0% vs 44.9% 🔬 INTERPRETATION The efficacy pattern supports a potential contribution of both EV and pembrolizumab. However, this was an ad hoc exploratory analysis, and comparisons should not be interpreted as confirmatory evidence of the independent contribution of each drug. ⭐ MY POINT OF VIEW | CLINICAL PEARL The question is evolving from whether perioperative EV + pembrolizumab works to understanding why the combination works—and which patients truly need both agents. The striking pCR difference and favorable OS signal reinforce the biological rationale for combining an ADC with immune checkpoint inhibition. 💡 But treatment intensification must always be balanced against toxicity, patient fitness and long-term benefit. 📌 EV + pembrolizumab is an established perioperative option for cisplatin-ineligible MIBC based on the parent KEYNOTE-905 trial. These exploratory findings add insight rather than establish a new treatment indication. 🌍 GU Oncology Community @gbanna74 @ravikanesvaran @urologysummit @tompowles1 @brian_rini @montypal @crisbergerot @DrDanielHeng @apolo_andrea @DrChoueiri @PGrivasMDPhD @TiansterZhang @HHammersMD @neerajaiims @amerseburger @sonpavde @drenriquegrande @scserendipity1 @Silke_Gillessen @EfstathiouEleni @BraunMDPhD @cdanicas @AOmlin @declangmurphy @salvolarosa @RenuEapen @seanmcbride @DrJaVallejo @ecancer @UrologyTimes @urotoday @wearemedsir @OpenMedicineHQ @UCSFCancer #BladderCancer #MIBC #GUOncology #ADC #ClinicalTrials
𝕏🎯 #ESMO26 EV 303 study update! Perioperative pembro was associated with numerically better EFS and OS compared with RC! 💯@OncoAlert @myESMO @tompowles1 @PGrivasMDPhD @urotoday @GuardConsortium https://t.co/cP3d2BKht4
𝕏🚨 What does enfortumab vedotin really add to perioperative pembrolizumab in MIBC? #ESMO2026 Exciting new data from KEYNOTE-905 at ESMO 2026! In 255 concurrently randomized, cisplatin-ineligible patients: 🔹 Pembrolizumab alone: pCR 25%, 2-year EFS 56%, EFS HR 0.71 vs cystectomy alone. 🔹 EV + pembrolizumab: pCR 59%, 2-year EFS 76%, EFS HR 0.40 vs cystectomy alone. A striking difference in pathological response! The key question: Which patients truly need EV in addition to immunotherapy? We urgently need predictive biomarkers to guide treatment selection and avoid unnecessary toxicity. 🎤 Happy to discuss optimal induction therapy in non-metastatic bladder cancer this Sunday at ESMO 2026! 📍 Special Symposium: Peri-operative management of urothelial cancer 🕟 Sunday, 16:30–16:45 | Barcelona Auditorium, Hall 9 Looking forward to an exciting discussion! 🔬 ESMO 2026 | KEYNOTE-905/EV-303 | Abstract 4733O @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
𝕏KN-905 ad hoc analysis: Pembro looks better than nothing, but EVP is clearly better than Pembro in this setting. #ESMO26 https://t.co/6Xow1gUnDH
𝕏Expert discussion from @MTeoMD at #ESMO26 https://t.co/G15EJSrhVT
𝕏KEYNOTE-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
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
⚡️ KEYNOTE-905 published in @NEJM: perioperative enfortumab vedotin + pembrolizumab vs surgery alone in cisplatin-ineligible MIBC (n=344). 2-year EFS: 74.7% vs 39.4% (HR 0.40) 2-year OS: 79.7% vs 63.1% (HR 0.50) pCR: 57.1% vs 8.6% The trial that supported FDA approval in
💫🌟KEYNOTE-905 is not just positive, it is practice-shifting in MIBC @NEJM @OncoAlert In cisplatin-ineligible patients, perioperative enfortumab vedotin + pembrolizumab delivers a magnitude of benefit we rarely see: 🔹 N = 344 🔹 2-year EFS: 74.7% vs 39.4% (HR 0.40) 🔹 2-year https://t.co/HiKDCcjhEi
Our friends from @GuardConsortium 🇪🇸Deliver another Great Informational Capsule, this time direct from #GU26 🇺🇸 We are proud to introduce our Colleague @mjuanfi81 Discussing the Presentation of: Pathological outcomes and disease-free survival (DFS) in KEYNOTE-905: Neoadjuvant
3 studies testing Perioperative immune bases therapy (EVP or Gem/Cis/Durva) in muscle invasive bladder all have shown an OS advantage vs standard of care. KN905 (EVP) is distinct in that it’s in a cisplatin ineligible population (accounting for the poor performance of the control
Cross trial comparison and where we are heading in MIBC @asco #gu26 @DrChoueiri @dr_yakupergun @brunolarvol @OncoAlert @OncBrothers
#ESMO25 had 4 GU trials in the Presidential plenary sessions! @myESMO On behalf our GU team, was proud to represent @CleClinicMD for 3/4! #IMvigor011, KN-905 and PSMAddition! Truly grateful to patients & families, my co- investigators & clinical research team for helping us
Incredible data from #KEYNOTE905 at #ESMO25 🔥 Enfortumab Vedotin + Pembrolizumab continues to reshape the landscape of bladder cancer. pCR 57% and EFS HR 0.4 / OS HR 0.5 - truly remarkable! @OncoAlert
1/2 KN905 Enfortumab Vedotin + Pembro continues to transform bladder cancer in spectacle fashion. In cisplatin ineligible operable disease it beats cystectomy with EFS HR 0.4, OS HR 0.5. pCR of 57% is much ⬆️ than anything before #ESMO25 pCR> 50% questions unselected surgery
2/2 this becomes standard of care here. Questions-How would this perform in a cisplatin eligible population? Better? Can ctDNA help? How many cycles are needed? B15 & VOLGA can help here.Finally, bladder sparing trials are needed to address the need for surgery @OncoAlert #ESMO25
Will this make the #ESMO2025 presidential ? There's a lot of excitement around the KEYNOTE-905 trial and results announced by press release. I have three main concerns/questions summarised in the slide. Looking forward to seeing real data and hopefully getting answers to those https://t.co/vruTnybMCi
KEYNOTE-905 Key Takeaways
Event-Free Survival — Primary Endpoint
Two-year EFS was 74.7% (95% CI 66.9-80.8) vs 39.4% (95% CI 31.0-47.8), HR 0.40 (95% CI 0.28-0.57), two-sided P<0.001. Median EFS was not reached (95% CI 37.3-NR) vs 15.7 months (95% CI 10.3-20.5). (NEJM / FDA, data cutoff 6 Jun 2025; median follow-up 25.6 months)
HR 0.40 — primary endpoint met 60% reduction in the risk of an event Source: Vulsteke C, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi:10.1056/NEJMoa2511674 →Overall Survival
Two-year OS was 79.7% vs 63.1%, HR 0.50 (95% CI 0.33-0.74), two-sided P<0.001. Median OS was not reached vs 41.7 months (95% CI 31.8-NR). (NEJM / FDA, data cutoff 6 Jun 2025; median follow-up 25.6 months)
HR 0.50 — key secondary endpoint met 50% reduction in the risk of death Source: Vulsteke C, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi:10.1056/NEJMoa2511674 →Pathological and Surgical Outcomes
Pathological complete response was 57.1% vs 8.6%; estimated difference 48.3% (95% CI 39.5-56.5), with non-surgical patients counted as non-responders in the intention-to-treat denominator. Pathological downstaging was 65.9% vs 12.6%; difference 53.1% (95% CI 44.0-61.2), and disease-free survival median not reached vs 23.6 months (HR 0.37; 95% CI 0.23-0.59). (NEJM / EAU 2026, data cutoff 6 Jun 2025; median follow-up 25.6 months)
Safety
Grade 3 or higher all-cause treatment-emergent adverse events occurred in 71.3% vs 45.9% (all-cause; any-grade 100% vs 64.8%). Grade 3 or higher drug-related events occurred in 45.5% grade ≥3 drug-related, combination arm only (no comparator figure exists - the control arm received no study drug). In the trial-specific safety population (167 vs 159), rash was reported in 54% any grade / 7% grade 3-4 and peripheral neuropathy in 39% any grade / 3% grade 3-4; pruritus 47% / 3%, alopecia 35% / 0.6%, fatigue 47% / 4.2%; serious AEs 58.1%; treatment discontinuation 37.1%. Laboratory increased glucose (laboratory abnormality) 72% any grade / 12% grade 3-4, vs 24% / 1.7% in the control arm. Importantly, surgery performed in 87.6% vs 89.7%; grade 3-5 adverse events during the surgical phase were LOWER with the combination (35.6% vs 45.9%). (NEJM / FDA label, data cutoff 6 Jun 2025; median follow-up 25.6 months)
Surgical-phase severe events were lower with the combination Source: Vulsteke C, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Apr 2;394(13):1257-1269. doi:10.1056/NEJMoa2511674 →Patient-Reported Outcomes (exploratory)
Patient-reported outcomes were exploratory and descriptive: within-arm mean change from baseline to post-surgery week 18, with no between-group statistical comparison. There was no clinically meaningful quality-of-life detriment from adding enfortumab vedotin plus pembrolizumab (FACT-G -2.73 vs -2.84; FACT-Bl-Cys total +1.31 vs +1.85). Sexual-function scores declined substantially in BOTH arms (-15.46 vs -17.88), a cystectomy effect rather than a drug effect. (Peter H. O'Donnell, ASCO 2026 Annual Meeting, data cutoff 6 Jun 2025; median follow-up 25.6 months)
Regulatory
✅ FDA approved November 21, 2025 for adults with MIBC ineligible for cisplatin, based on this trial. The indication was broadened on July 10, 2026 to all MIBC patients who are candidates for cystectomy, based on the sister trial KEYNOTE-B15/EV-304 — so the current label is not restricted to cisplatin-ineligible patients. (FDA, data cutoff 6 Jun 2025; median follow-up 25.6 months)
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Top KOLs Discussing KEYNOTE-905
KEYNOTE-905 Key Slides & Visuals
ESMO 2026 slides
More slides on this page
FDA Approval
KEYNOTE-905 Trial Design
KEYNOTE-905 (EV-303, NCT03924895) is a randomized, open-label phase 3 trial run by Merck Sharp & Dohme with Astellas Pharma and Pfizer (Seagen). It asked whether adding perioperative enfortumab vedotin plus pembrolizumab to radical cystectomy improves outcomes for patients with muscle-invasive bladder cancer who cannot receive cisplatin-based chemotherapy — a group that had historically proceeded straight to surgery with no proven systemic option. Results were presented at the ESMO 2025 Presidential Symposium (LBA2) and published in the New England Journal of Medicine.
The trial originally included a third pembrolizumab-alone arm, which was discontinued in 2022; randomization was then amended to 1:1. Total registered enrollment therefore exceeds the 344 patients randomized concurrently in the two reported arms.
Study Design
Randomized, open-label, multicenter phase 3. 344 patients randomized 1:1 (170 / 174).
Population
Adults with clinical stage T2-T4aN0M0 or T1-T4aN1M0 MIBC, ≥50% urothelial histology, ECOG 0-2, candidates for radical cystectomy. 281/344 (81.7%) cisplatin-ineligible; 63/344 (18.3%) declined cisplatin — the trial population is predominantly, but not exclusively, cisplatin-ineligible.
Interventions
Enfortumab vedotin 1.25 mg/kg days 1 and 8 every 3 weeks plus pembrolizumab 200 mg every 3 weeks for 3 neoadjuvant cycles, then 6 adjuvant cycles of enfortumab vedotin and up to 14 of pembrolizumab after cystectomy.
Comparator
radical cystectomy + pelvic lymph node dissection alone; no neoadjuvant therapy was permitted, but adjuvant immunotherapy per local guidelines was allowed and 16.7% (29/174) of control patients received adjuvant nivolumab.
Endpoints
Primary: event-free survival by blinded independent central review. Alpha-controlled secondaries in hierarchy: overall survival, then pathological complete response. Other secondaries: DFS, pathological downstaging, safety. Patient-reported outcomes were exploratory.
Lead Author
Christof Vulsteke. Presented at ESMO 2025 Presidential Symposium (LBA2).
KEYNOTE-905 in the News
KEYNOTE-905 FAQ
What did the KEYNOTE-905/EV-303 trial show?
In 344 patients with muscle-invasive bladder cancer who were cisplatin-ineligible or declined cisplatin, perioperative enfortumab vedotin plus pembrolizumab improved event-free survival (HR 0.40) and overall survival versus surgery alone. All figures and sources: At a Glance.
Is this regimen FDA approved?
Yes. The FDA approved it on November 21, 2025 for adults with MIBC ineligible for cisplatin, based on KEYNOTE-905/EV-303; on July 10, 2026 the indication was broadened to all MIBC patients who are candidates for cystectomy, based on KEYNOTE-B15/EV-304. See At a Glance.
How is KEYNOTE-905 different from KEYNOTE-B15?
KEYNOTE-905/EV-303 (NCT03924895) enrolled cisplatin-ineligible patients and compared the regimen with surgery alone; KEYNOTE-B15/EV-304 (NCT04700124) enrolled cisplatin-eligible patients and compared it with neoadjuvant gemcitabine plus cisplatin. Their results should not be cross-cited. See Trial Design.
What were the main side effects?
Grade 3 or higher adverse events were more frequent with the combination, with rash and peripheral neuropathy among the common events, while severe events during the surgical phase were lower with the combination. Rates and sources: At a Glance.
Did quality of life get worse with the added therapy?
No clinically meaningful quality-of-life detriment was seen in the exploratory, descriptive patient-reported outcomes; sexual-function scores declined in both arms, a cystectomy effect. See At a Glance.
Key KOL Sentiments - KEYNOTE-905
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 26, 2026.