FDA OKs Enfortumab Vedotin/Pembrolizumab Combo for Advanced Urothelial Cancer

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The FDA has granted approval to the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) for the treatment of patients with locally advanced or metastatic urothelial cancer (UC) who are not eligible to receive cisplatin-containing chemotherapy.¹

The approval is supported by findings are supported by efficacy and safety data from EV-302/KN-A39 (NCT04223856) where investigators evaluated the combination of enfortumab vedotin and pembrolizumab in this patient population.

Key findings from the trial showed that enfortumab and pembrolizumab showed encouraging safety and efficacy. Statistically significant improvements in both overall survival (OS) and progression-free survival (PFS) were demonstrated for enfortumab vedotin with pembrolizumab compared with platinum-based chemotherapy. Median OS was 31.5 months (95% CI, 25.4-not estimable) for patients who received enfortumab vedotin with pembrolizumab and 16.1 months (95% CI, 13.9-18.3) for those who received platinum-based chemotherapy (HR, 0.47; 95% CI, 0.38-0.58]; p <0.0001). Median PFS was 12.5 months (95% CI, 10.4-16.6) for patients who received enfortumab vedotin with pembrolizumab vs 6.3 months (95% CI, 6.2-6.5) for those who received platinum-based chemotherapy (HR 0.45; 95% CI, 0.38-0.54; p <0.0001).

Findings from the EV-302/KN-A39 study were presented at the 2023 ESMO Congress and published in the Annals of Oncology.² In the study, patients were randomized 1:1 (n = 886) to receive enfortumab vedotin plus pembrolizumab or chemotherapy. The median follow-up was 17.2 months. The confirmed overall response rate was 67.7% in the enfortumab vedotin and pembrolizumab arm compared with 44.4% in the chemotherapy arm.

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 55.9% of patients in the enfortumab vedotin plus pembrolizumab arm compared with 69.5% in the chemotherapy arm. The most common TRAEs were maculopapular rash (7.7%), hyperglycemia (5.0%), and neutropenia (4.8%) in the enfortumab vedotin plus pembrolizumab arm compared with anemia (31.4%), neutropenia (30%) and thrombocytopenia (19.4%) in the chemotherapy arm.

REFERENCES:

1. FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelia cancer. News release. U.S. Food & Drug Administration. December 15, 2023. Accessed December 15, 2023. http://tinyurl.com/346druu3

2. Powles TB, Perez Valderrama B, Gupta S, et al. LBA6 EV-302/keynote-A39: Open-label, Randomized Phase III study of enfortumab vedotin in combination with Pembrolizumab (EV+P) vs Chemotherapy (chemo) in previously untreated locally advanced metastatic urothelial carcinoma (LA/MUC). Annals of Oncology. 2023;34. doi:10.1016/j.annonc.2023.10.106