Cost-effectiveness of enfortumab vedotin plus pembrolizumab as a first-line treatment of locally advanced or metastatic urothelial carcinoma in the United States

OBJECTIVE: Enfortumab vedotin plus pembrolizumab (EV+Pem) was recently approved in the United States as the new first-line standard of care for locally advanced or metastatic urothelial carcinoma (la/mUC). We assessed the cost-effectiveness of EV+Pem as first-line treatment for la/mUC from a US third-party payer perspective, using the most recent database lock (data cutoff: 8 August 2024) from the Phase III EV302/KEYNOTE-A39 study (NCT04223856). METHODS: A partitioned survival model assessed the cost-effectiveness of EV+Pem versus gemcitabine and cisplatin/carboplatin followed by maintenance avelumab if not progressed (GP/GC ± Ave) in la/mUC patients. Standard and flexible spline parametric models were fitted to patient-level overall survival (OS) and progression-free survival (PFS) data from EV-302. Treatment discontinuation, utilities, and other clinical inputs were also based on EV-302. Cost inputs were sourced from literature or public databases. A cisplatin-eligible (Cis-E) subpopulation analysis compared EV+Pem versus nivolumab plus gemcitabine and cisplatin (Nivo + GP) and other platinum-based chemotherapies. A network meta-analysis based on the EV-302 and CheckMate-901 studies informed the OS and PFS hazard ratios for Nivo + GP versus EV+Pem. RESULTS: For the overall population, EV+Pem was projected to extend 2.58 life-years (LYs), or 1.76 quality-adjusted life-years (QALYs), versus GP/GC ± Ave, with an incremental cost-effectiveness ratio (ICER) of $180,631/QALY. Probabilistic sensitivity analyses (PSA) showed that EV+Pem had a 77% probability of being more cost-effective versus GP/GC ± Ave at a willingness-to-pay (WTP) threshold of $200,000/QALY. For the Cis-E subpopulation, EV+Pem was projected to extend 2.37 LYs (1.45 QALYs) versus Nivo + GP, with an ICER of $136,475/QALY. The PSA showed that EV+Pem had a 59% probability of being most cost-effective among all the treatment regimens considered, including platinum-based chemotherapies, at a WTP threshold of $200,000/QALY. CONCLUSIONS: EV+Pem is cost-effective compared to platinum-based regimens for the treatment of previously untreated la/mUC from a US third party payer perspective at a willingness-to-pay threshold of $200,000/QALY.