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FDA Expands Pembrolizumab and Enfortumab Vedotin for Perioperative Treatment of Muscle-Invasive Bladder Cancer

September 2026, Vol 16, No 5

On July 10, 2026, the FDA approved pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex), each in combination with enfortumab vedotin-ejfv (Padcev), as neoadjuvant treatment followed by adjuvant treatment after cystectomy for adults with muscle-invasive bladder cancer (MIBC). This expands the prior approval of the regimen from cisplatin-ineligible patients to all patients with MIBC who are candidates for cystectomy.

Approval was supported by KEYNOTE-B15/EV-304, a randomized trial of 808 patients with previously untreated MIBC who were eligible for cisplatin-based chemotherapy and planned for radical cystectomy. Patients received either perioperative pembrolizumab plus enfortumab vedotin-ejfv or neoadjuvant gemcitabine and cisplatin followed by surgery. The regimen significantly improved both event-free survival (EFS) and overall survival compared with chemotherapy, with median EFS not reached versus 48.5 months and a hazard ratio of 0.53. Median OS was also not reached in either arm, with a hazard ratio of 0.65.

The overall safety profile was consistent with prior studies of this combination in urothelial cancer. The prescribing information includes warnings and precautions for pembrolizumab-related immune-mediated adverse reactions, infusion reactions, transplant complications, and embryo-fetal toxicity, as well as enfortumab vedotin-related skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.

Source

  1. US Food and Drug Administration. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, each in combination with enfortumab vedotin-ejfv for muscle invasive bladder cancer. Accessed July 16, 2026. www.fda.gov/drugs/resources-information-approved-drugs/fda-ap proves-pembrolizumab-or-pembrolizumab-and-berahyaluronidase-alfa- pmph-each-enfortumab-vedotin

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