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

Matthew Galsky, MD, professor of medicine, hematology and medical oncology, professor of urology, director of Genitourinary Medical Oncology, codirector, the Center of Excellence for Bladder Cancer, and associate director, Translational Research at the Tisch Cancer Institute, Mount Sinai, discusses the FDA approval of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in patients with previously untreated, locally advanced or metastatic urothelial carcinoma.

Over the last few decades, there has been a shortage of efficiant first-line treatment options for patients with metastatic urothelial cancer, with platinum-based chemotherapy combinations being the primary first-line treatment approach, Galsky begins. Despite numerous efforts to improve upon this traditional regimen through phase 3 trials have been conducted, no demonstrable benefit with other regimens over platinum-based chemotherapy had been achieved, he says. However, 2 pivotal studies presented at the 2023 ESMO Congress demonstrated an improvement in survival beyond platinum-based chemotherapy alone, Galsky notes.

One of these was the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) which evaluated enfortumab vedotin plus pembrolizumab vs platinum-based chemotherapy, he states. The global, open-label, randomized trial showed a statistically significant and clinically meaningful survival benefit with the combination approach vs chemotherapy, as well as a tolerable safety profile, Galsky reports. At a median follow-up of 17.2 months, patients treated with enfortumab vedotin plus pembrolizumab experienced a 55% reduction in the risk of disease progression (HR, 0.45) and a 53% reduction in the risk of death (HR, 0.47) compared with those receiving chemotherapy. The median overall survival (OS) was 31.5 months (95% CI, 25.4-not reached) with the combination therapy vs 16.1 months (95% CI, 13.9-18.3) with chemotherapy.

Based on this research, the combination of enfortumab vedotin plus pembrolizumab was approved by the FDA for patients with locally advanced or metastatic urothelial cancer on December 15, 2023.

This regulatory decision represents a key advancement in the treatment of metastatic urothelial cancer, as it signifies the first substantial progress in decades, Galsky emphasizes. The magnitude of the survival benefit observed with the combination in this trial underscores its role as a new standard of care for first-line treatment in this patient population, he concludes.