First-Line Enfortumab Vedotin Plus Pembrolizumab vs Gemcitabine Plus Cisplatin for Metastatic Urothelial Carcinoma
Eusebio Luna Velasquez, Renil S. Titus, David-Dan Nguyen, Carlos Riveros, Aly-Khan Lalani, Dharam Kaushik, Guru P. Sonpavde, Petros Grivas, Christopher J. D. Wallis, Raj SatkunasivamImportance
Enfortumab vedotin plus pembrolizumab (EV/P) recently emerged as the preferred first-line treatment regimen for metastatic urothelial carcinoma (mUC), but evidence outside trial settings is relatively limited.
Objective
To evaluate outcomes associated with first-line EV/P compared with gemcitabine plus cisplatin (G/C) in patients with mUC.
Design, Setting, and Participants
This retrospective cohort study used the TriNetX database. Adults with mUC initiating first-line EV/P or G/C between September 2007 and September 2025 were included. Cohorts were propensity score matched for comparison by demographic characteristics, comorbidities, kidney function, and location of metastatic disease.
Main Outcomes and Measures
The primary outcome was overall survival (OS). Secondary outcomes included time to next treatment (TTNT), time to hospitalization within 90 days of treatment initiation (EHA), and adverse events (AEs). Outcomes were compared using Kaplan-Meier analysis and log rank test, reporting hazard ratios (HRs) and 95% CIs.
Results
The study included 4433 patients (1841 receiving EV/P and 2592 receiving G/C), with the EV/P group being significantly older (mean [SD] age, 70.6 [10.1] years vs 67.2 [10.6] years;
Conclusions and Relevance
In this retrospective cohort study of patients with mUC, EV/P was associated with longer OS, delayed TTNT, and lower time to EHA compared with G/C. These findings support the broader adoption of EV/P as first-line therapy in routine clinical practice.