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
In brief
Pembrolizumab did not significantly improve 5-year bladder cancer event-free survival
In 907 patients receiving chemotherapy and bladder removal, adding pembrolizumab produced 5-year event-free survival of 63.5%, compared with 61.9% with placebo, after about 5 years of follow-up. More patients had no cancer found at surgery with pembrolizumab, but overall survival was similar; the higher rate of severe side effects and lack of event-free survival benefit temper that finding.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 23 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- J Bedke, P Arkosy, H Nishiyama, H Mahammedi, C Vulsteke, M J Juan-Fita, et al.
- PMID
- 42918422
- DOI
- 10.1016/j.annonc.2026.10.106
Why clinicians should know about it
- Picked for Urology (paper of the day, 24 October 2026): Pembrolizumab added to chemo did not improve EFS
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.