Oncologic outcome and safety profile of first-line enfortumab vedotin plus pembrolizumab vs. conventional chemotherapy in advanced urothelial cancer.

Abstract

Aim: The aim of this multicenter study was to assess patient characteristics and short-term survival outcomes of first-line (1L) enfortumab vedotin plus pembrolizumab (EVP) as compared with conventional chemotherapy in locally advanced or metastatic urothelial carcinoma (la/mUC).

Methods: The database included 642 patients with la/mUC diagnosed between January 2008 and December 2025 at 12 collaborating hospitals. Baseline characteristics and follow-up data, including overall and organ-specific objective tumor response according to the RECIST v1.1, progression-free survival, and duration of response, were compared among the 1L regimens. Treatment-related adverse events (TRAEs) were graded according to the CTCAE v5.0 in patients treated with 1L EVP.

Results: The objective response and disease control rate were higher with 1L EVP than with chemotherapy (66% vs. 42% and 83% vs. 68%, respectively). The organ-specific response rate for liver metastatic lesions was 85%. Median progression-free survival (95% confidence interval) for 1L EVP, gemcitabine plus cisplatin, and gemcitabine plus carboplatin was 14.5 months (10.5-not determined), 10.5 months (8.4-13.3), and 9.2 months (6.7-14.2), respectively. In the safety analysis set including 40 patients, all-grade TRAEs occurred in 36 (90%) patients, including grade 1-2 events in 30 (75%) and grade 3-4 toxicities in 6 (15%). Grade 3-4 TRAEs included skin toxicity (7.5%), anorexia (5.0%), anemia (5.0%), gastrointestinal disorders (2.5%), renal dysfunction (2.5%), and interstitial lung disease (2.5%). The median number of administered EV cycles was 4 (range, 1-13), 5 (2-13), and 10 (4-13) in the overall, responder, and complete-response populations, respectively. EV dose modifications and interruptions were frequent in the initial 2 months but rare thereafter.

Conclusions: This multicenter study provides real-world evidence on short-term outcomes and safety with 1L EVP, highlighting its impact on the evolving treatment landscape for la/mUC.