Enfortumab vedotin plus pembrolizumab for previously untreated locally advanced or metastatic urothelial carcinoma: a cost-effectiveness analysis.

Background: Both the antibody-drug conjugate (ADC) enfortumab vedotin (EV) and programmed death-1 inhibitor pembrolizumab have been shown to provide survival benefits in patients previously treated with locally advanced or metastatic urothelial carcinoma (la/mUC). Cost-effectiveness is necessary to consider whether the increased efficacy of the two therapies will lead to higher prices for first-line treatment of previously untreated la/mUC. Objectives: To guide the choice of EV plus pembrolizumab or chemotherapy for patients with previously untreated la/mUC. Design: The cost-effective analysis. Methods: A Markov model was developed to simulate the lifetime of patients with previously untreated la/mUC to assess the overall cost and efficacy of EV plus pembrolizumab and chemotherapy based on the EV-302/KEYNOTE-A39 trial. Primary outcomes included total cost, life-years (LYs), quality-adjusted LYs (QALYs), the incremental cost-effectiveness ratio (ICER), and incremental net health benefits at the USA and Chinese willingness-to-pay threshold of $150,000/QALY and $35,173/QALY, respectively. Model stability was examined through sensitivity and subgroup analyses. Results: EV plus pembrolizumab and chemotherapy treatment regimens were associated with 2.07-2.16 and 1.04-1.06 QALYs with corresponding costs of $288,347-$532,362 and $24,773-$267,568, respectively. ICERs in the United States and China are $267,491/QALY and $254,339/QALY, respectively. The factors that most strongly influenced model outcomes in unidirectional sensitivity analyses were patient weight and the cost of EV. To achieve greater cost-effectiveness, EV costs would need to be reduced by over 75% and 10% in the United States and China, respectively. Conclusion: While first-line EV plus pembrolizumab has significant health benefits compared to chemotherapy for patients with previously untreated la/mUC, this regimen is not cost-effective at the current price in the United States or China.