Cost-Effectiveness of Perioperative Enfortumab Vedotin and Pembrolizumab for Bladder Cancer

Importance Although cisplatin-based neoadjuvant chemotherapy for patients with localized muscle-invasive blader cancer (MIBC) is associated with improved survival, nearly half of these patients are ineligible for cisplatin-based chemotherapy and historically proceed to radical cystectomy (RC) without neoadjuvant chemotherapy. Perioperative enfortumab vedotin (EV) plus pembrolizumab with RC is an alternative option, but little is known about its cost-effectiveness compared with surgery alone. Objective To evaluate the cost-effectiveness of perioperative EV plus pembrolizumab for cisplatin-ineligible patients with localized MIBC. Design, Setting, and Participants This economic evaluation developed a decision-analytic Markov model that compared neoadjuvant EV plus pembrolizumab followed by RC and adjuvant EV plus pembrolizumab (intervention arm) vs RC alone (control arm). The sample consisted of simulated patients with MIBC who were ineligible for or declined cisplatin-based neoadjuvant chemotherapy. The model was informed by efficacy and safety data from the KEYNOTE-905/EV-303 trial, which had a median (range) follow-up of 25.6 (11.8-53.7) months. Analyses were performed between October 2025 and August 2026. Intervention The 2 treatment strategies were (1) neoadjuvant EV plus pembrolizumab followed by RC and adjuvant EV plus pembrolizumab and (2) RC alone. Main Outcomes and Measures Outcomes included life-years, quality-adjusted life-years (QALYs), and direct medical costs estimated from a Medicare payer perspective over a 10-year horizon. Incremental cost-effectiveness ratio (ICER) was assessed against a willingness-to-pay threshold of $100 000 per QALY. Scenario, 1-way, and probabilistic sensitivity analyses were conducted. Results The model consisted of 10 000 patients (age at baseline, 73 years; 77 900 males [77.9%]). Over 10 years, adding perioperative EV plus pembrolizumab to treatment was associated with increased projected survival from 4.12 to 5.63 life-years per patient, quality-adjusted survival from 3.20 to 4.51 QALYs per patient, and total costs from $317 513 to $412 160. Higher upfront perioperative therapy costs were partially offset by lower postprogression treatment costs ($12 578 per patient for the intervention arm vs $238 729 per patient for the control arm). Perioperative EV plus pembrolizumab with RC achieved an ICER of $72 460 per QALY vs RC alone and therefore represented a cost-effective treatment approach. In 1-way and scenario sensitivity analyses, the cost-effectiveness result was sensitive to alternative assumptions for key factors, including time horizon length, adjuvant therapy utilization rates, patient age, postprogression treatment mix, drug costs, and health utility before disease progression. In the probabilistic sensitivity analysis, perioperative EV plus pembrolizumab with RC had a 53% probability of being cost-effective vs RC alone at the prespecified willingness-to-pay threshold of $100 000 per QALY. Conclusions and Relevance In this economic evaluation of a simulated cohort of patients with cisplatin-ineligible MIBC, clinical trial–informed modeling suggested that adopting the perioperative EV plus pembrolizumab intervention extends overall survival and quality-adjusted survival and is likely cost-effective in the US.