FDA Approves Perioperative Pembrolizumab-EV Regimen for MIBC

The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) and pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with enfortumab vedotin-ejfv (Padcev) for the perioperative treatment of adult patients with muscle-invasive bladder cancer (MIBC).

According to a news release from Merck, this regulatory milestone establishes the first and only PD-1 inhibitor plus antibody-drug conjugate (ADC) regimen approved for this patient population regardless of their eligibility for cisplatin-based chemotherapy.

The approval is based on data from the Phase 3 KEYNOTE-B15 (EV-304) trial, which evaluated the combination as a neoadjuvant treatment before radical cystectomy and pelvic lymph node dissection, followed by adjuvant treatment post-surgery. In patients eligible for cisplatin, the pembrolizumab combination reduced the risk of event-free survival (EFS) events by 47% compared to standard gemcitabine and cisplatin chemotherapy.

Furthermore, the regimen reduced the risk of death by 35%, with a pathologic complete response (pCR) rate of 55.8% compared to 32.5% in the chemotherapy arm.

Matthew Galsky, MD, Director of Genitourinary Medical Oncology at Mount Sinai Tisch Cancer Center, emphasized in the news release the clinical significance of this shift in care. “This shift away from traditional cisplatin-based chemotherapy, which has been recommended for eligible patients for more than 20 years, provides important new treatment options for individuals with muscle-invasive bladder cancer regardless of cisplatin eligibility," Galsky stated.

In a recent interview with Oncology Nursing News, Galsky further noted that this approval addresses a critical unmet need for patients who previously had few systemic options.

"Not only does this treatment path allow patients who previously could not receive systemic therapy based on the risk versus benefits to have a systemic therapy option to reduce the risk of recurrence and improve overall survival," Galsky explained, "but it's actually also better than the standard treatment that we've been using for 20-plus years."

For the oncology nursing team, managing the complexity of this regimen is paramount. The treatment involves multiple phases, starting with four cycles of neoadjuvant pembrolizumab and enfortumab vedotin, followed by surgery, and then up to 13 cycles of adjuvant pembrolizumab and five cycles of adjuvant enfortumab vedotin.

Galsky highlighted the necessity of comprehensive patient education regarding this timeline. "We do like to outline the full course of treatment from the beginning because it is a lot of steps, it is a long program of treatment not without potential risks," he noted.

Clinicians must remain vigilant for immune-mediated adverse reactions and chemotherapy-related toxicities. The most common adverse reactions reported in the KEYNOTE-B15 trial included rash (63%), fatigue (48%), pruritus (46%), peripheral neuropathy (43%), and diarrhea (36%). Serious adverse reactions occurred in approximately 27% of patients during the neoadjuvant phase and 35% during the adjuvant phase.

Galsky concluded that this regimen now "becomes a standard treatment for all of our patients with muscle-invasive bladder cancer for whom the risks versus benefits are perceived to be appropriate based on their comorbidities and a shared medical decision."

Reference

Merck. FDA Approves KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph), Each With Padcev® (enfortumab vedotin-ejfv), as Treatment Before and After Surgery for Adults With Muscle-Invasive Bladder Cancer (MIBC). July 10, 2026. Accessed July 22, 2026.