On December 15, 2023, enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) was approved for patients with locally advanced or metastatic urothelial cancer.1,2
Supporting Efficacy Data
Approval was based on findings in the open-label EV-302 trial (ClinicalTrials.gov identifier NCT04223856). In this study, 886 patients with no prior systemic therapy for advanced disease were randomly assigned to receive enfortumab vedotin with pembrolizumab (n = 442) or platinum-based chemotherapy (n = 446) consisting of gemcitabine plus either cisplatin or carboplatin.
OF NOTE
Enfortumab vedotin has a boxed warning for serious skin reactions. Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.The median overall survival was 31.5 months (95% confidence interval [CI] = 25.4 months to not estimable) with enfortumab vedotin plus pembrolizumab vs 16.1 months (95% CI = 13.9–18.3 months) with chemotherapy (hazard ratio [HR] = 0.47, 95% CI = 0.38–0.58, P < .0001). The median progression-free survival was 12.5 months (95% CI = 10.4–16.6 months) with enfortumab vedotin plus pembrolizumab vs 6.3 months (95% CI = 6.2–6.5 months) with chemotherapy (HR = 0.45, 95% CI = 0.38–0.54, P < .0001).
How It Is Used
The recommended enfortumab vedotin dose when given with pembrolizumab is 1.25 mg/kg on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. The recommended pembrolizumab dose when given with enfortumab vedotin is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 2 years of therapy.
Safety Profile
Among 873 patients in the safety population of the EV-302 trial, the most common adverse events of any grade with enfortumab plus pembrolizumab were rash, peripheral neuropathy, fatigue, and pruritus. Enfortumab vedotin has a boxed warning for serious skin reactions. Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
REFERENCES
1. Padcev (enfortumab vedotin), Astellas, December 2023. Available at www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed January 2, 2024.
2. Keytruda (pembrolizumab), Merck, December 2023. Available at www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed January 2, 2024.
