Real-world outcomes with first-line enfortumab vedotin plus pembrolizumab versus gemcitabine plus cisplatin for metastatic urothelial carcinoma

The phase 3 EV-302 trial showed superior overall survival (OS) and progression-free survival (PFS) with enfortumab vedotin plus pembrolizumab (EV/P) compared with platinum-based chemotherapy as first-line treatment for metastatic urothelial carcinoma (mUC), but evidence outside trial settings is limited. A retrospective cohort study using th TriNetX database compared real-world outcomes with first-line EV/P versus gemcitabine plus cisplatin (G/C) in patients with mUC. The study included 4433 patients: 1841 receiving EV/P and 2592 receiving G/C. The cohorts were propensity score matched for comparison by demographic characteristics, comorbidities, kidney function, and location of metastatic disease. First-line EV/P was associated with lower risk of death (HR 0.70; 95% CI 0.63-0.79), longer median OS (20 versus 11 months), lower risk of hospitalization within 90 days of treatment initiation (HR 0.73; 95% CI 0.64-0.83), and longer median time to next treatment (35 versus 10 months; HR 0.49; 95% CI 0.39-0.61). The OS benefit with EV/P over G/C was statistically significant in almost all subgroupss. Receipt of EV/P as first-line treatment was associated with higher rates of rash, hyperglycemia, and hypothyroidism but fewer cytopenias and gastrointestinal toxic effects. The authors conclude that these findings support the broader adoption of EV/P as first-line therapy for mUC in routine clinical practice.