Outcomes of Older Patients on Enfortumab Vedotin for Urothelial Carcinoma

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 remain limited. This study compares efficacy and safety outcomes between patients aged 70 years or older and those aged less than 70 years receiving EV therapy using real-world data.

METHODS

This single-center, retrospective cohort study reviewed patients with aUC who received at least 1 dose of EV (alone or with pembrolizumab) in any line of treatment between December 1, 2019, and August 1, 2025, at the Huntsman Cancer Institute. Primary end points 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. Median OS and PFS were estimated using Kaplan-Meier methods and compared using Cox regression. Other outcomes were presented descriptively.

RESULTS

There were 84 adult patients with a median age of 71.6 years included. Baseline characteristics were similar across age groups, except for higher male predominance and baseline hemoglobin A1c levels in those aged 70 years and older. OS and PFS did not significantly differ in both unadjusted and adjusted analyses, with an HR of 0.89 (95% CI, 0.49-1.61) and an HR of 1.06 (95% CI, 0.61-1.85), respectively, among patients aged at least 70 years compared with those aged less than 70 years. Patients aged at least 70 years started at a reduced dose (1 mg/kg) more frequently than those less than 70 years (33.3% vs 10.3%; P = .012). Fewer older patients maintained RDI greater than or equal to 80% throughout therapy (80% vs 94.9%; P = .044). Dose delays and cancellations were more common in the under-70-years group (74.4% vs 53.3%; P = .046), while patients at least 70 years old more often required dose reduction (48.9% vs 30.8%, P = .071). Overall, toxicity was the most common reason for dose modification. Grade 2 or higher neuropathy (28.9% vs 25.6%; P = .74) and dermatologic toxicity (24.4% vs 17.9%; P = .47) did not differ significantly between patients aged 70 years or older and those aged less than 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 outcomes similar to those of younger patients, supporting the use of individualized dosing strategies in this population.