Outcomes of enfortumab vedotin plus pembrolizumab in patients with advanced urothelial cancer and severe renal dysfunction

BACKGROUND AND OBJECTIVE: Enfortumab vedotin plus pembrolizumab (EV+P) is now the standard first-line (1L) therapy for advanced urothelial cancer (aUC), based on improved survival in the EV-302 trial. However, the trial excluded patients with creatinine clearance (CrCl) <30 ml/min, leaving an evidence gap for patients with severely impaired renal function. To address this, we evaluated outcomes of EV+P in patients with aUC and CrCl <30 ml/min using real-world data. METHODS: We conducted a real-world retrospective cohort study using a database derived from electronic health records from approximately 280 U.S. oncology practices. Adults with aUC initiating 1L EV+P between April 2023 and December 2024 were included. Outcomes included overall survival (OS), progression-free survival (PFS), and EV interruption-free survival (IFS), stratified by baseline CrCl (≥30 vs. <30 ml/min). We constructed multivariable Cox models adjusted for demographics, clinical factors, and potential confounders. RESULTS: Among 462 eligible patients who initiated 1L EV+P between April 2023 and December 2024, 65 (14.1%) had CrCl <30 ml/min. In multivariable Cox models, severely impaired renal function was not associated with worse overall survival (OS) (adjusted HR [aHR] = 0.95, 95% CI [0.61-1.49]; P = 0.84), progression-free survival (PFS) (aHR = 0.70 [0.47-1.06]; P = 0.092), or EV interruption-free survival (IFS) (aHR = 0.82 [0.48-1.38]; P = 0.45). CONCLUSIONS: These real-world findings indicate that patients with CrCl <30 ml/min experienced outcomes comparable to those with higher renal function, providing important evidence in a population that is often excluded from clinical trials.