Efficacy and Safety of Two-Weekly Enfortumab Vedotin in Combination With Pembrolizumab for Advanced Urothelial Carcinoma.

INTRODUCTION

Enfortumab vedotin (EV) plus pembrolizumab (PEM) is a standard first-line therapy for advanced urothelial carcinoma (UC), but EV-related toxicities frequently lead to treatment modification or discontinuation. This study evaluated the efficacy and safety of a two-weekly EV dosing schedule combined with PEM in real-world clinical practice.

METHODS

This retrospective observational study included treatment-naïve patients with metastatic UC who received two-weekly EV (1.25 mg/kg) plus PEM. Treatment response, survival outcomes, adverse events (AEs), and treatment modifications were assessed.

RESULTS

Twenty patients were included. The objective response rate was 75%, including complete responses in 10% of patients. Median progression-free survival and overall survival were not reached; 6-and 12-month progression-free survival rates were 74.4% and 68.2%, respectively, and 6-and 12-month overall survival rates were 89.7% and 84.1%. Any-grade AEs occurred in 85% of patients, and grade ≥ 3 AEs occurred in 35% of patients. The most common AEs were skin reaction, peripheral sensory neuropathy, and liver dysfunction. No grade ≥ 3 cutaneous toxicities or peripheral neuropathy were observed.

CONCLUSIONS

Two-weekly EV administration combined with PEM showed favorable antitumor activity with manageable toxicity in patients with advanced UC. This dose-modified regimen may represent a feasible treatment option in real-world settings, although prospective validation is warranted.