Real-world efficacy and safety outcomes of older adult patients on enfortumab vedotin for urothelial carcinoma.

Abstract

e13767 Background: The treatment landscape for advanced urothelial carcinoma (aUC) has undergone a significant transformation since the FDA approval of enfortumab vedotin (EV) in 2019. Although results from pivotal trials have been practice-changing, older adults were underrepresented in these studies, and data including these patients remains limited. This study compares efficacy and safety outcomes between patients aged ≥70 years and those aged < 70 years receiving EV therapy using real-world data. Methods: This single-center, retrospective cohort study reviewed patients with aUC who received at least one dose of EV (alone or with pembrolizumab) in any line of treatment between 12/01/2019 and 08/01/2025 at the Huntsman Cancer Institute. Primary endpoints include overall survival (OS) and progression free survival (PFS) stratified by age group. Additional outcomes include incidence and reasons for dose modification, relative dose intensity (RDI), and frequency of treatment-related toxicities. Progression and incidence/severity of toxicities were determined by the primary treating physician and collected via electronic medical record documentation. RDI was calculated using the total delivered dose divided by the total standard dose multiplied by 100. Median OS and PFS were estimated using Kaplan-Meier methods and compared using Cox regression, adjusting for sex, de novo metastatic disease, pre-existing diabetes and baseline neutrophil-to-lymphocyte ratio. Other outcomes were presented descriptively. Results: 84 adult patients with a median age of 71.6 years were included. Baseline characteristics were similar across age groups, except for higher male predominance and baseline HbA1c levels in those 70 and older. OS and PFS did not significantly differ in both unadjusted and adjusted analysis, with HR 0.89 (95%CI 0.49, 1.61) and HR 1.06 (95%CI 0.61, 1.85), respectively, among patients aged ≥70 years compared to < 70 years. Patients aged ≥70 years started at a reduced dose (1 mg/kg) more frequently than those < 70 years (33.3% vs 10.3%, p = 0.012). Fewer older patients maintained RDI ≥80% throughout therapy (80% vs 94.9%, p = 0.044). Dose delays and cancellations were more common in < 70 years group (74.4% vs 53.3%, p=0.046), while patients ≥70 years old more often required dose reduction (48.9% vs 30.8%, p=0.071). Overall, toxicity was the most common reason for dose modification. Grade 2+ neuropathy (28.9% vs 25.6%, p = 0.74) and dermatologic toxicity (24.4% vs 17.9%, p = 0.47) did not differ significantly between patients aged ≥70 years compared to < 70 years, respectively. Conclusions: This study provides real-world evidence on efficacy, dosing, and tolerability of EV therapy in older adults with aUC. Older patients with aUC receiving EV therapy achieved similar outcomes to younger patients, supporting the use of individualized dosing strategies in this population.