On November 21, 2025, the FDA approved pembrolizumab (Keytruda), or pembrolizumab with berahyaluronidase alfa-pmph (Keytruda Qlex), in combination with enfortumab vedotin-ejfv (Padcev), as neoadjuvant therapy followed by adjuvant therapy after cystectomy for adults with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy.1
Efficacy was demonstrated in the KEYNOTE-905/EV-303 trial (NCT03924895), an open-label, randomized study in 344 patients with untreated MIBC who were candidates for radical cystectomy with pelvic lymph node dissection but were ineligible for or declined cisplatin. Patients receiving pembrolizumab and enfortumab vedotin-ejfv before and after surgery showed significant improvements in event-free survival (EFS) and overall survival (OS) compared with surgery alone. Median EFS was not reached (NR) in the treatment arm versus 15.7 months in the surgery-only arm (hazard ratio [HR], 0.40; P<.0001). Median OS was NR versus 41.7 months in the respective arms (HR, 0.50; P=.0002).
Safety profiles were consistent with prior studies. Pembrolizumab warnings include immune-mediated adverse reactions and infusion-related reactions, while enfortumab vedotin-ejfv warnings include skin reactions, hyperglycemia, and interstitial lung disease.
Reference
- US Food and Drug Administration. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. November 21, 2025. Accessed November 30, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer