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Markus Eckstein· @Markuseckstein3 · X·· 3 days agoScore90

KEYNOTE-905

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🔬 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

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Conference abstracts
4733Omatched by Proffered paper 1: Genitourinary tumour, renal and urothelial

Perioperative pembrolizumab (pembro) or enfortumab vedotin (EV) plus pembro in pts with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: ad hoc analysis from KEYNOTE-905

https://esmocongress.esmo.org
NCT03924895NCT03924895matched by - **标题 / Title:** Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

- **标题 / Title:** Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

https://esmocongress.esmo.org

Source: Markus Eckstein · x.com

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