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.