Dr Galsky on the FDA Approval of Pembrolizumab Plus Enfortumab Vedotin in MIBC

“[This approval] has implications in [terms of] referrals in that there doesn't need to be this filtering of patients who might not be appropriate for systemic therapy or rather cisplatin-based chemotherapy. All patients should now be referred from urology to medical oncology because we have a regimen that applies to all patients for whom the risks vs benefits are consistent with their goals and wishes.”

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 the significance of the July 2026 FDA approval of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex), each 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).

The approval was supported by data from the phase 3 KEYNOTE-B15/EV-304 study (NCT04700124). Findings from KEYNOTE-B15 showed that patients who received perioperative pembrolizumab and enfortumab vedotin (n = 405) experienced a median event-free survival that was not reached (NR; 95% CI, NR-NR) compared with 48.5 months (95% CI, 43.3-NR) among patients who received neoadjuvant gemcitabine and cisplatin (n = 403; HR, 0.53; 95% CI, 0.41-0.70; P < .0001). The median overall survival was NR in either arm (HR, 0.65; 95% CI, 0.48-0.89; P = .0029).

Previously, data from phase 3 KEYNOTE-905/EV-303 trial (NCT03924895) established enfortumab vedotin plus pembrolizumab as an effective perioperative treatment option in chemotherapy-ineligible patients with MIBC, Galsky began. The study demonstrated that this regimen provides meaningful clinical benefit in patients who are unable to receive cisplatin-based chemotherapy, representing the first neoadjuvant systemic therapy specifically validated for this historically underserved population, he noted.

Prior to these findings, treatment planning for patients with MIBC often centered on determining whether an individual was eligible to receive cisplatin-based chemotherapy, Galsky explained. Because neoadjuvant cisplatin-containing regimens had long been the standard of care, careful consideration of the potential benefits and risks associated with cisplatin was required, he said.

The availability of perioperative enfortumab vedotin plus pembrolizumab has fundamentally changed this treatment paradigm, Galsky said. Rather than separating patients into cisplatin-eligible and cisplatin-ineligible groups when discussing neoadjuvant therapy, an evidence-based systemic treatment option can be offered to virtually all patients with MIBC, provided the regimen aligns with their individual goals of care and overall health status, he added. This simplifies treatment discussions and expands access to perioperative systemic therapy for a broader patient population, he concluded.