Dr Galsky on Data Supporting the FDA Approval of Perioperative EV/Pembrolizumab in MIBC

“The primary end point showed an improvement in EFS, with an HR of 0.53. OS was also shown to be improved with perioperative EV/pembrolizumab, with an HR of 0.65.”

Matthew Galsky, MD, a professor of medicine (hematology and medical oncology), director of genitourinary medical oncology, codirector of the Center of Excellence for Bladder Cancer, and deputy director at the Mount Sinai Tisch Cancer Center, discussed notable data from the phase 3 KEYNOTE-B15/EV-304 study (NCT04700124) that supported the July 2026 FDA approval of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with enfortumab vedotin-ejfv (Padcev) as neoadjuvant treatment followed by adjuvant treatment following cystectomy in adult patients with muscle-invasive bladder cancer (MIBC).

KEYNOTE-B15/EV-304 evaluated the efficacy of perioperative enfortumab vedotin plus pembrolizumab compared with the current standard of care in patients with clinically localized MIBC, Galsky began. This large, randomized study was designed to determine whether integrating an antibody-drug conjugate and immune checkpoint inhibitor throughout the perioperative period could improve outcomes over conventional cisplatin-based chemotherapy, he noted.

Patients were randomly assigned to receive one of two treatment strategies. In the experimental arm, patients underwent a comprehensive perioperative regimen consisting of neoadjuvant enfortumab vedotin plus pembrolizumab before radical cystectomy, followed by adjuvant enfortumab vedotin plus pembrolizumab after surgery, and an additional period of pembrolizumab monotherapy. The control arm received the established standard of care: neoadjuvant gemcitabine plus cisplatin followed by radical cystectomy.

The primary end point of the study was event-free survival (EFS), while key secondary end points included overall survival (OS) and pathologic complete response (pCR), Galsky explained. The trial met its primary objective, demonstrating a significant improvement in EFS with the perioperative enfortumab vedotin plus pembrolizumab regimen (HR, 0.53; 95% CI, 0.41-0.70; P < .0001), which translated to a 47% reduction in the risk of disease recurrence, progression, or death compared with standard neoadjuvant chemotherapy.

The combination therapy also produced a meaningful improvement in OS (HR, 0.6; 95% CI, 0.48-0.89; P = .0029), indicating a 35% reduction in the risk of death. In addition, the regimen achieved a pathologic complete response rate of 55.8%, reflecting a substantial proportion of patients with no residual invasive disease identified at the time of cystectomy, Galsky concluded.