First-line Enfortumab Vedotin Plus Pembrolizumab in Platinum-ineligible Advanced Urothelial Carcinoma

Platinum-ineligible patients with locally advanced or metastatic urothelial carcinoma represent a clinically vulnerable population with limited treatment options and poor historical outcomes. Although first-line enfortumab vedotin plus pembrolizumab has become a new standard treatment, evidence in platinum-ineligible patients remains limited. This study described the real-world clinical course of platinum-ineligible patients treated with first-line enfortumab vedotin plus pembrolizumab within a consecutive cohort.

This retrospective single-center study included 40 consecutive patients with locally advanced or metastatic urothelial carcinoma who initiated first-line enfortumab vedotin plus pembrolizumab between December 2024 and March 2026. Platinum eligibility was determined using prespecified creatinine clearance-based criteria. Tumor response, progression-free survival, overall survival, treatment-related adverse events, and individual treatment courses were evaluated descriptively.

Among 40 patients, eight were classified as platinum ineligible. Tumor response was evaluable in six platinum-ineligible patients, of whom one achieved complete response and three achieved partial response. Median progression-free survival and overall survival were not reached in the platinum-ineligible subgroup. Grade ≥3 treatment-related adverse events were infrequent. The swimmer plot demonstrated heterogeneous clinical trajectories, including early discontinuation in some patients and prolonged treatment exposure or off-treatment disease control in others.

First-line enfortumab vedotin plus pembrolizumab showed encouraging clinical activity and acceptable tolerability in selected platinum-ineligible patients with advanced urothelial carcinoma. Given the small subgroup size, these findings should be interpreted as descriptive and hypothesis-generating.