Real-world use and effectiveness of first-line enfortumab vedotin (EV) with pembrolizumab (P) in patients with advanced urothelial carcinoma (aUC).

Abstract

692 Background: EV+P significantly improved overall survival (OS) compared with platinum-based chemotherapy in the EV-302 trial and is now established as the new first-line (1L) standard of care for patients (pts) with aUC [PMID: 38446675]. Recent data show that EV+P has become the most commonly used 1L regimen for aUC [PMID: 39174408]. However, there are limited data on the real-world survival outcomes with EV+P. Herein, we sought to assess the use and effectiveness of 1L EV+P in a large real-world dataset. Methods: This study used the US-based, electronic health record-derived deidentified Flatiron Health Research Database. Eligibility: diagnosis of aUC between 4/1/2014 and 6/23/2025 and receipt of 1L treatment with EV+P. Pts on clinical trials were excluded. The data cut-off date was 6/30/2025. Uptake of EV+P by year of 1L initiation was summarized using frequency and percentages. Median time to next therapy (TTNT) was defined as time from 1L initiation to 2L initiation or death and censored at the lost to follow-up. Median OS was defined as time from the 1L initiation to death and censored at the lost to follow-up. The Kaplan-Meier method was used to estimate median TTNT and OS, and their 95% confidence intervals (CIs). Results: Of 15,236 pts with aUC in the dataset, 10,960 had 1L treatment information available, of whom 745 received 1L EV+P and included in the analysis. The start date for 1L EV+P was between 2/28/2020 and 6/24/2025. Median age was 74 years (IQR 67 – 80), 74% were male, and 66% were non-Hispanic White. Uptake of EV+P increased over time, comprising 62% of 1L regimens started in 2025. Uptake of EV+P by year of 1L initiation is shown in Table. With a median follow-up time of 10.3 months, median TTNT was 11 months (95% CI 9.5 – 12), with 328 events (44%), and median OS was 17 months (95% CI 15 – 21), with 254 pts (34%) having an event. Conclusions: This is the largest analysis to date evaluating real-world uptake and survival outcomes with 1L EV+P in the US. EV+P demonstrates significant real-world uptake. However, real-world survival outcomes do not match those seen in the EV-302 trial, which suggests a difference in the patient characteristics in real-world than those enrolled in the EV-302 trial. These data may assist with patient counseling and prognostication. Limitations include the retrospective design, missingness, and real-world dataset. Uptake of EV+P by year of 1L initiation in pts with aUC. Year N 1L EV+P n (%) 2020 1006 2 (0.2) 2021 930 3 (0.3) 2022 965 4 (0.4) 2023 919 142 (15) 2024 821 420 (51) 2025 302 186 (62)