Dr Galsky on the Safety Profile for Enfortumab Vedotin Plus Pembrolizumab in MIBC

“Enfortumab vedotin plus pembrolizumab has been integrated as standard treatment for first-line metastatic urothelial cancer now for several years, and many clinicians have had some experience with this regimen.”

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 safety profile of perioperative pembrolizumab (Keytruda) in combination with enfortumab vedotin-ejfv (Padcev) in muscle-invasive bladder cancer (MIBC) following its July 2026 FDA approval.

Enfortumab vedotin plus pembrolizumab has become an established standard-of-care regimen for the first-line treatment of metastatic urothelial carcinoma, providing many medical oncologists with substantial clinical experience managing this combination, Galsky began. As its use expands into earlier-stage disease, understanding its unique safety profile has become increasingly important, he noted. Although the regimen differs significantly from traditional cisplatin-based chemotherapy, available data indicate that the overall incidence of severe treatment-related toxicities is comparable between the two approaches, he said.

Findings from the phase 3 KEYNOTE-B15/EV-304 study (NCT04700124) trial suggest that the principal distinction between enfortumab vedotin plus pembrolizumab and cisplatin-based chemotherapy lies not in the frequency of high-grade adverse effects (AEs) but in the nature of the toxicities encountered, Galsky explained. Rather than one regimen being universally more toxic than the other, each is associated with a distinct spectrum of AEs effects that requires different monitoring and management strategies, he said.

Several treatment-related AEs are particularly important for clinicians to recognize when administering enfortumab vedotin plus pembrolizumab, Galsky said. Cutaneous reactions, including rash, are among the most common AEs associated with enfortumab vedotin, he said. Although most cases are mild and can be effectively managed with topical therapies, more severe skin reactions may occur and warrant close clinical monitoring, he explained. Peripheral neuropathy is another well-recognized toxicity of enfortumab vedotin and tends to develop gradually with cumulative dosing, he noted. Early recognition of neuropathic symptoms is important because dose modifications may help prevent progression to more severe or persistent symptoms, he added.

A small subset of patients may also develop hyperglycemia during treatment, making periodic monitoring of blood glucose levels an important component of patient management, Galsky said. In addition, because pembrolizumab is an immune checkpoint inhibitor, clinicians must remain vigilant for immune-related AEs affecting a variety of organ systems, including the skin, gastrointestinal tract, liver, endocrine glands, and lungs, he concluded.