778 Background: Enfortumab vedotin (EV) plus pembrolizumab (Pem) has demonstrated superior efficacy in clinical trials for metastatic urothelial carcinoma (mUC). To assess the performance of this regimen in routine practice, we conducted real-world comparative outcomes analysis versus gemcitabine plus platinum (GEM + Plat) using the TriNetX Research Network. Methods: Adults (≥18 years) with stage IV mUC between 2019 and 2025 were included. Cohorts were defined by index therapy with EV + Pem or GEM + Plat. Propensity-score matching (1:1) was used to match on age, sex, race, ethnicity, metastatic location, and comorbidities. Outcomes were analyzed within 720 days post-index using Kaplan–Meier and risk estimates. Results: Matching yielded 325 patients per arm, and the cohorts were well-balanced (mean age 70 years, 75% male). Overall survival favored EV + Pem, with 12-month survival of 72.5% versus 62.8% (p = 0.017) and 24-month survival of 57.1% versus 48.2% (p = 0.010) (Table 1). Time to next treatment was markedly longer with EV + Pem (HR 0.08, 95% CI 0.06–0.10, p < 0.001), with only 64 of 325 EV + Pem patients initiating subsequent therapy within 24 months. The risk of treatment-related adverse-event proxies (neuropathy, dermatitis, or pruritus) was higher with EV + Pem (p < 0.001), while inpatient/ED visits were less frequent at both six months (p = 0.001) and twelve months (p = 0.008). Laboratory comparisons at 0–12 weeks showed no difference in mean eGFR, creatinine, or albumin, while hemoglobin was higher with EV + Pem (p< 0.0001). Conclusions: In this large propensity-matched real-world cohort, first-line EV + Pem was associated with improved overall survival, prolonged treatment durability, and lower health-care utilization compared with GEM + Plat, albeit with higher adverse effects. Real-world outcomes: EV + Pem vs GEM + Plat. Endpoint EV + Pem GEM + Plat HR * /OR @ (95% CI) P 12-month OS (%) 72.5 62.8 0.70 (0.52–0.94) 0.017 24-month OS (%) 57.1 48.2 0.70 (0.53–0.92) 0.010 Adverse Effect proxies (%) 45.1 27.8 2.71 (2.01–3.64) <0.001 Inpatient/ED visits 6 mo (%) 58.2 71.1 0.76 (0.63–0.92) 0.001 Inpatient/ED visits 12 mo (%) 65.8 78.2 0.67 (0.65–0.94) 0.008 Hb < 10 g/dL (%) 46.5 80.0 0.47 (0.38–0.57) <0.001 eGFR (mean) 63.8 65.1 – 0.59 Albumin (g/dL, mean) 3.57 3.53 – 0.41 AST (U/L, mean) 31.2 26.1 – 0.002 ALT (U/L, mean) 27.4 22.7 – 0.03 *Hazard Ratio. @ Odds Ratio.
Jafry et al. (Sun,) studied this question.