Study compares Enfortumab Vedotin + Pembrolizumab vs Gemcitabine + Cisplatin in Urothelial Carcinoma

First-line enfortumab vedotin plus pembrolizumab (EV/P) was associated with longer survival and delayed subsequent therapy compared with gemcitabine plus cisplatin (G/C) in patients with metastatic urothelial carcinoma (mUC), according to a retrospective cohort study published in JAMA Network Open.

The study evaluated whether outcomes reported with EV/P in clinical trials were also seen in routine clinical practice. The authors noted that evidence outside trial settings has been limited, particularly because trial populations may exclude patients with poorer performance status or significant comorbidities.

Researchers used the TriNetX database to identify adults with mUC who started first-line EV/P or G/C between September 2007 and September 2025. The study included 4433 patients, including 1841 who received EV/P and 2592 who received G/C. Cohorts were propensity score matched by demographic characteristics, comorbidities, kidney function, and metastatic disease location.

First-line EV/P was associated with lower risk of death compared with G/C (hazard ratio [HR], 0.70; 95% CI, 0.63-0.79). Median overall survival (OS) was 20 months with EV/P compared with 11 months with G/C. EV/P was also associated with longer time to next treatment (median, 35 vs 10 months; HR, 0.49; 95% CI, 0.39-0.61) and lower risk of early hospitalization within 90 days of treatment initiation (HR, 0.73; 95% CI, 0.64-0.83).

The adverse event profiles differed between groups. EV/P was associated with higher risks of rash, diarrhea, hyperglycemia, and hypothyroidism and lower risks of fatigue, nausea, anemia, thrombocytopenia, and neutropenia compared with G/C. The authors concluded that the findings reinforce the effectiveness of EV/P in routine clinical practice and support broader adoption as first-line therapy for mUC, while noting limitations including the retrospective design and potential residual confounding.

Sources: Velasquez EL, Titus RS, Nguyen D, et al. First-line enfortumab vedotin plus pembrolizumab vs gemcitabine plus cisplatin for metastatic urothelial carcinoma. JAMA Netw Open. 2026;9(7):e2621032. doi:10.1001/jamanetworkopen.2026.21032