🚨⭐ #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

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