Annals of oncology : official journal of the European Society for Medical Oncology · 2026
Perioperative pembrolizumab or placebo plus neoadjuvant cisplatin and gemcitabine in participants with muscle-invasive bladder cancer who are eligible for cisplatin: the double-blind, phase III KEYNOTE-866 study.
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Bedke J, Arkosy P, Nishiyama H, Mahammedi H, Vulsteke C, Juan-Fita M J, Antonyan I, Didas O, Verzoni E, Atduev V, Rodriguez-Vida A, Oh J J, Kang S-H, Peer A, Zukov R, Zurawksi B, Gümüş M, Steinberg G D, Olah J, Abadie-Lacourtoisie S, Jain N, Franco S, Moreno B Homet, Hoimes C J, Siefker-Radtke A
Аннотация
BACKGROUND: Perioperative PD-(L)1 inhibitors, either combined with cisplatin-based chemotherapy or enfortumab vedotin, have improved outcomes in patients with muscle-invasive bladder cancer (MIBC) who are cisplatin eligible. The double-blind, phase III KEYNOTE-866 study evaluated perioperative (neoadjuvant and adjuvant) pembrolizumab versus placebo added to neoadjuvant cisplatin plus gemcitabine (chemotherapy) and radical cystectomy with pelvic lymph node dissection (cystectomy) in MIBC.
PATIENTS AND METHODS: Eligible participants were aged ≥18 years, had centrally assessed clinical stage T2-T4aN0M0 or T1-T4aN1M0 MIBC with ≥50% urothelial histology, and were eligible for cisplatin-based chemotherapy and cystectomy. Participants were randomly assigned (1:1) to neoadjuvant pembrolizumab or placebo plus chemotherapy every 3 weeks for 4 cycles, followed by cystectomy, and adjuvant pembrolizumab or placebo every 3 weeks for 13 cycles (pembrolizumab or placebo group, respectively). Primary end point was event-free survival (EFS) by investigator assessment. Pathological complete response (pCR) rate by blinded independent central pathological review and overall survival (OS) were key secondary end points. Safety was a secondary end point.
RESULTS: Overall, 907 participants were randomly assigned (pembrolizumab, n = 453; placebo, n = 454). Median follow-up was 60.9 months (range, 40.7-78.7). At 60 months, the estimated EFS rate was 63.5% with pembrolizumab versus 61.9% with placebo (hazard ratio 0.88; 95% CI 0.71-1.10; one-sided P = 0.1366). The pCR rate was 44.4% versus 35.8% (estimated difference 8.9%; 95% CI 2.5-15.1); median OS was not reached in both groups (hazard ratio 1.00; 95% CI 0.79-1.27). Treatment-emergent adverse events occurred in 99.8% of participants in the pembrolizumab group (grade ≥3 in 80.2%) and 98.7% in the placebo group (grade ≥3 in 75.1%).
CONCLUSIONS: The addition of perioperative pembrolizumab to neoadjuvant chemotherapy and cystectomy did not confer a statistically significant EFS benefit in participants with MIBC who are cisplatin eligible. The safety profile of pembrolizumab was manageable and consistent with prior reports.
PATIENTS AND METHODS: Eligible participants were aged ≥18 years, had centrally assessed clinical stage T2-T4aN0M0 or T1-T4aN1M0 MIBC with ≥50% urothelial histology, and were eligible for cisplatin-based chemotherapy and cystectomy. Participants were randomly assigned (1:1) to neoadjuvant pembrolizumab or placebo plus chemotherapy every 3 weeks for 4 cycles, followed by cystectomy, and adjuvant pembrolizumab or placebo every 3 weeks for 13 cycles (pembrolizumab or placebo group, respectively). Primary end point was event-free survival (EFS) by investigator assessment. Pathological complete response (pCR) rate by blinded independent central pathological review and overall survival (OS) were key secondary end points. Safety was a secondary end point.
RESULTS: Overall, 907 participants were randomly assigned (pembrolizumab, n = 453; placebo, n = 454). Median follow-up was 60.9 months (range, 40.7-78.7). At 60 months, the estimated EFS rate was 63.5% with pembrolizumab versus 61.9% with placebo (hazard ratio 0.88; 95% CI 0.71-1.10; one-sided P = 0.1366). The pCR rate was 44.4% versus 35.8% (estimated difference 8.9%; 95% CI 2.5-15.1); median OS was not reached in both groups (hazard ratio 1.00; 95% CI 0.79-1.27). Treatment-emergent adverse events occurred in 99.8% of participants in the pembrolizumab group (grade ≥3 in 80.2%) and 98.7% in the placebo group (grade ≥3 in 75.1%).
CONCLUSIONS: The addition of perioperative pembrolizumab to neoadjuvant chemotherapy and cystectomy did not confer a statistically significant EFS benefit in participants with MIBC who are cisplatin eligible. The safety profile of pembrolizumab was manageable and consistent with prior reports.