🚨⭐🟠 #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