Dr Lee on the Efficacy of Enfortumab Vedotin Plus Pembrolizumab in Urothelial Cancer

“Probably the most important [bladder cancer treatment update] is the approval of enfortumab vedotin plus pembrolizumab as frontline therapy for locally advanced and metastatic urothelial carcinoma.”

John K. Lee, MD, PhD, associate professor-in-residence, Division of Hematology/Oncology, Department of Medicine; the Institute for Urologic Oncology, Department of Urology, the David Geffen School of Medicine, UCLA Heath, discusses the significance of the phase 3 EV-302 trial (NCT04223856) investigating enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in the first-line setting in patients with locally advanced or metastatic urothelial cancer.

One of the most important recent advancements in bladder cancer management has been the 2023 FDA approval of enfortumab vedotin plus pembrolizumab as frontline therapy for patients with locally advanced or metastatic urothelial carcinoma, Lee begins. For decades, the standard first-line treatment for this patient population was platinum-based chemotherapy, which long remained the cornerstone of therapy despite limited success in improving disease outcomes, Lee describes.

The pivotal EV-302 trial combined the antibody-drug conjugate enfortumab vedotin with the immune checkpoint inhibitor pembrolizumab and compared this regimen with standard chemotherapy. Enfortumab vedotin plus pembrolizumab generated substantial improvements in overall survival (OS) and progression-free survival (PFS), Lee notes. The median PFS was 12.5 months (95% CI, 10.4-16.6) with the combination (n = 442) vs 6.3 months (95% CI, 6.2-6.5) with chemotherapy (n = 444; HR, 0.45; 95% CI, 0.38-0.54; P < .001). The median OS in these respective arms was 31.5 months (95% CI, 25.4-not reached [NR]) and 16.1 months (95% CI, 13.9-18.3 [HR, 0.47; 95% CI, 0.38-0.58; P < .001]).

Furthermore, the overall response rate with the combination was 67.7% (95% CI, 63.1%-72.1%) vs 44.4% (95% CI, 39.7%-49.2%) with chemotherapy. Complete responses were observed in 29.1% and 12.5% of patients in the combination (n = 437) and chemotherapy arms (n = 441), respectively. The median duration of response was NR (95% CI, 20.2 months-NR) with enfortumab vedotin plus pembrolizumab vs 7.0 months (95% CI, 6.2-10.2) with chemotherapy. These findings have established enfortumab vedotin plus pembrolizumab as a superior therapeutic option over chemotherapy in patients with advanced or metastatic urothelial cancer, irrespective of cisplatin eligibility, Lee concludes.