Expanded Perioperative Use for Pembrolizumab in Bladder Cancer

The FDA approved perioperative use of pembrolizumab (Keytruda, Merck) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex, Merck), each with enfortumab vedotin-ejfv (Padcev, Astellas Pharma), for adults with muscle-invasive bladder cancer who are candidates for cystectomy.

The approval covers neoadjuvant treatment before surgery followed by adjuvant treatment after cystectomy. This extends the prior approval for the regimen from patients who were cisplatin-ineligible to all adults with muscle-invasive bladder cancer who are surgical candidates.

Efficacy was evaluated in KEYNOTE-B15/EV-304, an open-label, randomized, active-controlled, multicenter trial that enrolled 808 patients with previously untreated muscle-invasive bladder cancer who were candidates for radical cystectomy with pelvic lymph node dissection and eligible for cisplatin-based chemotherapy.

Patients were randomly assigned 1:1 to perioperative pembrolizumab plus enfortumab vedotin or neoadjuvant gemcitabine and cisplatin followed by surgery. The pembrolizumab-enfortumab vedotin regimen significantly improved event-free survival and overall survival. Median event-free survival was not reached with the combination and was 48.5 months with gemcitabine-cisplatin (hazard ratio [HR], 0.53; 95% CI, 0.41-0.70; P<.0001). Median overall survival was not reached in either group (HR, 0.65; 95% CI, 0.48-0.89; P=.0029).

For cisplatin-eligible patients, the recommended neoadjuvant regimen includes pembrolizumab 200mg intravenously every 3 weeks or 400mg intravenously every 6 weeks with enfortumab vedotin 1.25mg/kg (up to a maximum of 125mg for patients ≥100kg) intravenously on days 1 and 8 of a 21-day cycle for 4 cycles. Enfortumab vedotin continues for 5 additional adjuvant cycles with pembrolizumab after surgery, followed by pembrolizumab as a single agent.

The FDA said the review used Project Orbis and was completed 5 weeks ahead of the agency goal date. The action broadens the perioperative option of pembrolizumab plus enfortumab vedotin-ejfv to all adults with muscle-invasive bladder cancer who are candidates for cystectomy, expanding beyond the prior cisplatin-ineligible population. 

Sources: FDA. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. July 10, 2026.