Background: EV-302/KEYNOTE-A39 (NCT04223856) is a phase 3, open-label, randomized, global study comparing EV+P with platinum-based chemotherapy for first-line (1L) treatment of patients (pts) with la/mUC regardless of cisplatin eligibility or PD-L1 expression status. In EV-302, EV+P demonstrated a statistically significant and clinically meaningful benefit compared with platinum-based chemotherapy for the dual primary endpoints of progression-free survival (PFS) (hazard ratio [HR]: 0.45; P<0.00001) and overall survival (OS) (HR: 0.47; P<0.00001) in the overall pt population (Powles ESMO 2023). Here we present results not previously presented of prespecified subgroup analyses. Methods: Pts with previously untreated la/mUC were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg; Days 1 and 8; IV) and P (200 mg; Day 1; IV) or gemcitabine with cisplatin or carboplatin. Select secondary endpoints included confirmed objective response rate (cORR), duration of response, and safety. For PFS and OS, an HR between treatment arms was estimated using a stratified Cox proportional hazards regression model controlling for the stratification factors (cisplatin eligibility, PD-L1 status [high/low], liver metastases [yes/no]) for each predefined subgroup. Results: 886 pts (EV+P: 442, chemotherapy: 444) were randomized; baseline pt and disease characteristics were balanced between groups. PFS and OS were prolonged for EV+P among prespecified subgroups, including race, cisplatin eligibility, PD-L1 expression, metastatic site, liver involvement, and renal function. Select subgroup data not previously presented for OS are presented in the Table. Kaplan-Meier curves for PFS (liver metastases, cisplatin eligibility, and PD-L1 status) and OS (liver metastases) will also be presented. Conclusions: EV+P significantly improved outcomes in pts with previously untreated la/mUC compared with chemotherapy; OS benefit was consistently observed across select prespecified subgroups, including those historically associated with poor prognosis. The results of these subgroup analyses support the findings of the primary analysis, which indicate that EV+P is a potential new standard of care for 1L la/mUC. Clinical trial information: NCT04223856.

NR, not reached.