Keytruda plus Padcev OK'd for broader use in muscle-invasive bladder cancer

FDA has expanded the indication for Keytruda (pembrolizumab) or Keytuda Qlex (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with Padcev (enfortumab vedotin-ejfv), for the perioperative treatment of muscle-invasive bladder cancer (MIBC). Previously approved only for patients who were ineligible for cisplatin, the regimen is now indicated for all adults with MIBC who are candidates for radical cystectomy.

The expanded indication establishes the combination as a perioperative treatment option regardless of cisplatin eligibility, giving clinicians an alternative to cisplatin-based neoadjuvant chemotherapy for patients undergoing cystectomy.

Approval was based on the phase 3 KEYNOTE-B15/EV-304 trial in 808 patients with previously untreated MIBC who were eligible for cisplatin-based chemotherapy. Compared with neoadjuvant gemcitabine plus cisplatin followed by surgery, perioperative pembrolizumab plus enfortumab vedotin reduced the risk of disease recurrence, progression, or death by 47% and reduced the risk of death by 35%. Median event-free survival was not reached with the pembrolizumab regimen versus 48.5 months with chemotherapy.

The safety profile was consistent with previous studies of the combination. Clinicians should monitor for immune-mediated adverse reactions associated with pembrolizumab and for skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, and ocular disorders associated with enfortumab vedotin.

"For almost 25 years, cisplatin-based neoadjuvant chemotherapy was the standard of care for approximately half of patients with muscle-invasive bladder cancer who were eligible to receive platinum-based treatment. Results from KEYNOTE-B15 further support that a perioperative approach with pembrolizumab plus enfortumab vedotin can significantly improve survival compared to neoadjuvant chemotherapy in cis-eligible patients with muscle-invasive bladder cancer – setting the stage for a new treatment standard in this disease setting," said Matthew D. Galsky, MD, Director of Genitourinary Medical Oncology and Co-Director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.

Sources: FDA. (2026 July 10). FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer; Merck. (2026 July 10). FDA approves KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), each with PADCEV (enfortumab vedotin-ejfv), for adults with muscle-invasive bladder cancer regardless of cisplatin eligibility