Cost-effectiveness analysis of first-line (1L) therapies for advanced urothelial carcinoma (aUC) from a U.S. payer perspective.

4589 Background: Recent years have seen a shift in aUC management following approval of enfortumab vedotin–pembrolizumab (EV-P) and gemcitabine/cisplatin plus nivolumab (GC-NIVO) as first-line therapies. Despite improved clinical outcomes, their relative economic value remains uncertain. Herein, we conducted a cost-effectiveness analysis of current 1L regimens in aUC from a U. S. payer perspective using 2026 pricing. Methods: A partitioned survival model with three health states (progression-free PF, progressed disease PD, and death) was developed over a 10-year horizon from a U. S. payer perspective. Analyses focused on cisplatin-eligible patients. Survival data were reconstructed from published Kaplan–Meier curves and extrapolated using parametric survival models. Treatment dosing, schedules, and duration were modeled according to trial protocols. Patients receiving gemcitabine/cisplatin without progression were modeled to receive avelumab maintenance (GC→AVEL). Subsequent-line therapy costs were applied at incident progression, and grade ≥3 adverse event costs and disutilities were applied as one-time events. Drug acquisition costs (2026 USD) were based on average sales prices from the Centers for Medicare & Medicaid Services. Costs and quality-adjusted life years (QALYs) were discounted at 3% annually. Incremental cost-effectiveness ratios (ICERs) and net monetary benefit (NMB) were evaluated at willingness-to-pay (WTP) thresholds of 100, 000, 150, 000, and 200, 000 per QALY. Parameter uncertainty was characterized using probabilistic sensitivity analysis. Results: In the base-case analysis, total discounted costs and QALYs were 90, 269 and 1. 62 for GC→AVEL, 131, 836 and 2. 09 for GC-NIVO, and 1, 451, 885 and 2. 77 for EV-P. Compared with GC→AVEL, GC-NIVO gained 0. 46 QALYs at an incremental cost of 41, 567, resulting in an ICER of 89, 501 per QALY and positive NMB across all evaluated WTP thresholds. Compared with GC→AVEL, EV-P gained 1. 15 QALYs at an incremental cost of 1. 36 million (ICER 1. 19 million per QALY). Compared with GC-NIVO, EV-P gained 0. 68 QALYs at an incremental cost of 1. 32 million (ICER 1. 93 million per QALY), exceeding all evaluated WTP thresholds. In a scenario analysis limiting EV-P to 10 treatment cycles, total costs decreased to 287, 360, with ICERs of 172, 000/QALY versus GC→AVEL and 225, 000/QALY versus GC-NIVO, remaining above the 150, 000/QALY threshold. Conclusions: Using updated 2026 pricing, GC-NIVO is likely to be the most cost-effective first-line regimen for cisplatin-eligible patients with aUC. EV-P offers the greatest clinical benefit but is not cost-effective at current prices. A major limitation of this study is cross-trial variability in study populations and design, limiting the validity of head-to-head economic comparisons.