Real-world Outcomes of First-line Enfortumab Vedotin Plus Pembrolizumab in Elderly Patients With Advanced Urothelial Carcinoma

Abstract

Background/Aim: Evidence regarding first-line enfortumab vedotin plus pembrolizumab (EVP) in elderly patients with advanced urothelial carcinoma (UC), particularly those aged ≥80 years, remains limited. This study evaluated the real-world effectiveness, safety, and treatment feasibility of EVP stratified by age. Patients and Methods: We retrospectively analyzed 40 consecutive patients with unresectable locally advanced or metastatic UC who received first-line EVP at a single institution between December 2024 and April 2026. Outcomes were assessed using predefined age cutoffs of 75 and 80 years. Tumor response was evaluated according to RECIST version 1.1 and adverse events according to CTCAE version 5.0. Results: The median age was 76.2 years, 22 patients (55.0%) were aged ≥75 years and 11 (27.5%) were aged ≥80 years. Patients in the older group were more likely to have lymph node-only disease and lower creatinine clearance. Objective response rates were 52.9% and 77.3% in patients aged <75 and ≥75 years and 64.3% and 72.7% in those aged <80 and ≥80 years, respectively. Grade ≥3 treatment-related adverse events occurred in nine patients (22.5%) overall. Median treatment duration was 2.7 months. At a median follow-up of 7.7 months, no significant differences in progression-free or overall survival were observed according to either age cutoff. Several elderly responders had no documented disease progression at their most recent post-discontinuation assessment; however, treatment duration and follow-up after discontinuation were limited. Conclusion: In this small, selected real-world cohort, first-line EVP showed preliminary antitumor activity and feasible treatment delivery in elderly patients with advanced UC, including very elderly patients. These findings should be considered hypothesis-generating and require validation in larger studies with longer follow-up and standardized geriatric assessment.