The FDA has approved Padcev (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate from Pfizer, for perioperative use in adults with muscle-invasive bladder cancer who cannot receive cisplatin, to be given alongside pembrolizumab as neoadjuvant and adjuvant therapy after cystectomy.

This approval introduces a new option with the potential to improve perioperative outcomes and long-term survival for patients at high risk of recurrence after cystectomy, where few alternatives existed for decades.

In the trial results, Padcev plus pembrolizumab reduced the risk of tumor recurrence, progression, or death by 60% compared with surgery alone, with median event-free survival not yet reached for the combination versus 15.7 months for surgery alone.

The combination also cut the risk of death by 50%, delivering about a 79.7% two-year survival probability for Padcev plus pembrolizumab versus 63.1% with surgery alone, with median overall survival not yet reached for the combo arm.

Dr. Matthew Galsky of Mount Sinai Tisch Cancer Center notes that cisplatin-ineligible patients with MIBC often have limited options, and this approval could be a practice-changing advance.

The approval is grounded in the Phase III KEYNOTE-905 trial, which randomized patients to receive neoadjuvant and adjuvant pembrolizumab alone, surgery alone, or Padcev plus pembrolizumab as the experimental arm.