Cost-Effectiveness of Enfortumab Vedotin and Pembrolizumab for First-Line Metastatic Urothelial Cancer in the United States

Objectives The EV-302 trial demonstrated that the combination of enfortumab vedotin and pembrolizumab (EV+P) significantly improved progression-free and overall survival in patients with metastatic urothelial cancer. However, the economic value of this regimen remains uncertain. Our study aims to evaluate the cost-effectiveness of EV+P versus platinum-based chemotherapy as first-line treatment for metastatic urothelial cancer from the US payer perspective. Methods We developed a cohort state-transition model to simulate the lifetime costs and effectiveness of a cohort of 69-year-olds with metastatic urothelial cancer, resembling those in the EV-302 trial. Costs and utilities were derived from published literature to calculate the quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio for EV+P relative to chemotherapy. We conducted deterministic and probabilistic sensitivity analyses to identify factors influencing the cost-effectiveness. Results In the base case, the chemotherapy strategy costs $80 874, yielding 1.26 QALYs and 1.69 life years. The EV+P strategy costs $752 637, yielding 2.54 QALYs and 3.31 life years. This resulted in an incremental cost-effectiveness ratio of $525 239/QALY and $414 927/life year. To achieve cost-effectiveness at a $150 000/QALY threshold, the price of the combination therapy would need to be reduced by 76%. A probabilistic sensitivity analysis indicated that EV+P was cost-effective in 0% of the simulations. Conclusions Although EV+P therapy is effective, it is not cost-effective at its current price as a first-line therapy in the United States at a cost-effectiveness threshold of $150 000/QALY. A substantial reduction in its drug cost is required to be cost-effective at commonly accepted willingness-to-pay thresholds.