FDA Alert

FDA Approves Keytruda-Based Regimens for Muscle-Invasive Bladder Cancer

Edited by:
Ashton L. Stahl

Key Highlights

  • The FDA approved Keytruda or Keytruda Qlex, each with Padcev, for adults with muscle-invasive bladder cancer.
  • The approval expands use from cisplatin-ineligible patients to all cystectomy candidates with MIBC.
  • KEYNOTE-B15/EV-304 showed statistically significant improvements in event-free survival and overall survival.

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

The approval was based on KEYNOTE-B15/EV-304, an open-label, randomized, active-controlled, multicenter trial of 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 received perioperative pembrolizumab plus enfortumab vedotin-ejfv or neoadjuvant gemcitabine plus cisplatin followed by surgery. The median event-free survival was not reached in the pembrolizumab combination arm vs 48.5 months in the comparator arm (hazard ratio, 0.53; 95% CI, 0.41-0.70; P < .0001). Median overall survival was not reached in either arm, with an HR of 0.65 (95% CI, 0.48-0.89; P = .0029).

The overall safety profile of pembrolizumab with enfortumab vedotin-ejfv was similar to that observed in prior trials of this combination in urothelial cancer. The pembrolizumab prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. Enfortumab vedotin-ejfv includes warnings and precautions for skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.

For cisplatin-eligible patients, the recommended neoadjuvant pembrolizumab dose is 200 mg IV every 3 weeks or 400 mg IV every 6 weeks with enfortumab vedotin-ejfv 1.25 mg/kg IV on days 1 and 8 of a 21-day cycle for 4 cycles, totaling 12 weeks. In the adjuvant phase, enfortumab vedotin-ejfv continues for 5 additional cycles every 3 weeks with pembrolizumab, followed by pembrolizumab as a single agent for an overall adjuvant duration of 39 weeks.

References

Food and Drug Administration. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. FDA. Published July 10, 2026. Accessed July 15, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-or-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-enfortumab-vedotin