Real-World Efficacy and Safety of Frontline Enfortumab Vedotin Plus Pembrolizumab in Metastatic Urothelial Carcinoma: A Multicenter Study and Review of the Literature

Abstract

Background Enfortumab vedotin plus pembrolizumab (EV + P) is an established standard of care for metastatic urothelial carcinoma; however, real-world data remain limited. We evaluated clinical outcomes in patients treated in the frontline metastatic setting. Patients and Methods The primary endpoint was objective response rate (ORR); secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and safety. Median follow-up and survival outcomes were estimated using reverse and standard Kaplan-Meier methods and Cox regression analyses. Result Overall, 160 patients were included, with 148 (92.5%) receiving EV + P in the 1L. The median follow-up was 14 months. In the 1L, the median PFS was 12 months (95% CI, 6.4-17.6). The CR rate was 14.9% and the PR rate was 54.1%, resulting in an ORR of 69.0%. SD and PD were observed in 16.9% and 14.1% of patients, respectively. Among patients achieving CR or PR, the median duration of response was 20 months (95% CI, 11.3-28.6). In univariate analyses for PFS, patients with upper urinary tract tumors had significantly shorter PFS compared with those with lower urinary tract tumors (5 vs. 20 months, P = .004). Patients with ECOG PS >= 2 had shorter PFS than those with ECOG PS <= 1 (3 vs. 16 months; P = .002). De novo metastatic disease was associated with worse PFS (6 vs. 23 months, P = .07). In the 1L EV + P cohort, 12- and 24-month OS rates were 73.8% and 57.7%, respectively. In the >= 2-line cohort (n = 12), the ORR was 66.7%, with PR in 58.4% and CR in 8.3%; SD and PD were observed in 8.3% and 25.0% of patients, respectively. Overall, 80.6% of patients experienced at >= 1 treatment-related adverse event (TRAEs) of any grade, and 19 patients (13.7%) developed grade 3 to 4 TRAEs. Conclusions In this real-world cohort, EV + P demonstrated meaningful clinical activity and manageable safety as frontline therapy, consistent with EV-302.