Efficacy of Enfortumab Vedotin After Platinum Chemotherapy and Pembrolizumab in Metastatic Urothelial Carcinoma: A Multicenter Real-World Analysis of the ARON-2EV Cohort

Background and objective: Enfortumab vedotin (EV) has demonstrated efficacy in metastatic urothelial carcinoma (mUC) following treatment with platinum-based chemotherapy (PBC) and PD-1/PD-L1 inhibitors, including pembrolizumab (PEM). Our aim was to assess real-world clinical outcomes of EV in patients with mUC previously treated with PBC followed by pembrolizumab (PBC/PEM). Methods: ARON-2EV is an international, multicenter, retrospective study examining the real-world use of EV in patients with mUC. This analysis included 401 patients with mUC treated with EV following PBC/PEM. Primary endpoints were overall survival (OS), time on treatment (ToT), and the overall response rate (ORR). Secondary objectives included evaluation of clinical factors associated with outcomes and exploration of the impact of prior PEM outcomes. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and χ2 tests, Pearson's correlation coefficients, and Cox analyses. Key findings and limitations: Median OS was 12.3 mo (95% confidence interval [CI] 9.9–14.3), median ToT was 10.4 mo (95% CI 9.0–12.2), and the ORR was 45%. Prior response to PEM was significantly correlated with subsequent outcomes on EV. In the group who experienced progressive disease (PD) on prior PEM, the ORR was 35%. Major limitations are related to the retrospective study design. Conclusions: EV has consistent real-world efficacy in patients with mUC following sequential treatment with PBC/PEM. These results support the utility of EV in diverse clinical scenarios and suggest an association between prior PEM outcomes and subsequent EV efficacy. Patient summary: The ARON-2EV project is collecting real-world data for patients with metastatic cancer of the urinary tract who are being treated with a drug called enfortumab vedotin (EV) in multiple centers worldwide. Our results show that EV has consistent efficacy in these patients after previous treatment with platinum-based chemotherapy followed by pembrolizumab. The results also suggest an association between a patient's response to pembrolizumab and their subsequent response to EV.