Impact of Impaired Renal Function on the Efficacy and Safety of Enfortumab Vedotin Monotherapy in a Multicenter Real-World Cohort of Patients With Metastatic Urothelial Cancer: YUSHIMA Study

Abstract

Introduction: Enfortumab vedotin (EV) has become a standard of care for patients with metastatic urothelial cancer (mUC). However, the impact of impaired renal function on its efficacy and safety remains unclear, especially in patients with severe renal impairment who are considered unfit for platinum-based chemotherapy.

Patients and methods: This multicenter retrospective study included 115 patients with mUC who were treated with EV monotherapy after progression on platinum-based chemotherapy and immune checkpoint inhibitors. Patients were stratified into 3 groups based on pretreatment estimated glomerular filtration rate (eGFR, mL/min/1.73 m²): Preserved (eGFR ≥ 45, n = 65), Moderately Impaired (30 ≤ eGFR < 45, n = 36), and Severely Impaired (eGFR < 30, n = 14). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared among the 3 groups.

Results: The median follow-up time following after the initiation of EV treatment was 7.2 months. Although relative dose intensity (RDI) was lower in the Severely Impaired group, ORR (P = .62), PFS (P = .33), and OS (P = .81) were not significantly different among the 3 groups. There was no significant difference in the incidence of any grade TRAEs among the 3 groups (P = .22). For grade ≥ 3 TRAEs, its incidence was significantly different overall (P = .040), but no pairwise differences were found after Bonferroni correction. Among patients with RDI ≥ 80%, impaired renal function was not significantly associated with the incidence of TRAEs.

Conclusions: EV monotherapy demonstrated comparable efficacy and safety regardless of renal function in patients with mUC. Our findings suggest that impaired renal function alone may not warrant avoiding EV monotherapy or routinely reducing its dose. Moreover, EV monotherapy can be effective and well-tolerated even in patients with eGFR < 30 who are considered unfit for platinum-based chemotherapy.

Keywords: Enfortumab vedotin; Metastatic urothelial cancer; Overall survival; Progression-free survival; Real world outcomes; Relative dose intensity.