Exploratory subgroup analyses of EV-302: a phase III global study to evaluate enfortumab vedotin in combination with pembrolizumab versus chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma

作者：Michiel S. van der Heijden, Thomas Powles, Shilpa Gupta, Y. Loriot, Matt D. Galsky, Begoña P. Valderrama, S.S. Sridhar, Evan Y. Yu, Gopa Iyer, Eiji Kikuchi, D Castellano, Jean Hoffman‐Censits, Alexandra Drakaki, Nataliya Mar, J.P. Maroto Rey, Christof Vulsteke, Waddah Arafat, I. Duran, Nancy A. Dawson, Umang Swami, Seema Rao Gorla, Blanca Homet Moreno, Xuesong Yu, Yingdong Lu, Jens Bedke · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105544 · 被引用次数：17 · 研究领域：Bladder and Urothelial Cancer Treatments、Esophageal Cancer Research and Treatment、Urinary and Genital Oncology Studies

BACKGROUND: In the phase III EV-302 study (NCT04223856), enfortumab vedotin (EV) plus pembrolizumab (P) demonstrated superior efficacy and safety versus platinum-based chemotherapy in patients with previously untreated locally advanced/metastatic urothelial cancer (la/mUC). We report the efficacy of EV+P in prespecified subgroups, including those defined by cisplatin eligibility status, the presence or absence of liver metastases, and metastatic disease sites. METHODS: Patients with previously untreated la/mUC were randomly assigned 1 : 1 to receive either EV 1.25 mg/kg and pembrolizumab 200 mg, or gemcitabine plus cisplatin or carboplatin, all intravenously. The two primary endpoints were progression-free survival (PFS) and overall survival (OS). Confirmed objective response rate was one of the secondary endpoints. RESULTS: Overall, 886 patients were randomized: 442 to EV+P and 444 to chemotherapy. Baseline characteristics were balanced across treatment groups. Efficacy and safety data for the intention-to-treat (ITT) population, along with PFS and OS data for cisplatin-eligible and -ineligible patients, were previously published (Powles et al. N Eng J Med, 2024). In this analysis, EV+P showed benefit across prespecified subgroups that was consistent with the ITT population. OS benefit in the EV+P arm versus chemotherapy was seen across all subgroups, including patients with liver metastases (OS 19.1 versus 10.1 months), patients without liver metastases [OS not estimable (N...