Abstract
Patients with BRAF V600E-mutant metastatic colorectal cancer have poor prognosis, and the value of first-line targeted combination therapies remains uncertain. We evaluated the cost-effectiveness of encorafenib plus cetuximab with or without chemotherapy compared with standard chemotherapy, using clinical outcomes from a phase 3 randomized trial. A partitioned survival model with long-term extrapolation was applied to estimate lifetime costs and health outcomes from a United States payer perspective. Although both targeted regimens improved survival compared with standard chemotherapy, they were associated with substantially higher costs. Consequently, neither targeted strategy was cost-effective at commonly used willingness-to-pay thresholds under current pricing. These findings demonstrate that clinically meaningful survival gains may not translate into economic value in first-line settings. This study underscores the importance of incorporating economic evidence into early treatment adoption decisions and highlights the need for pricing approaches that better align costs with patient benefit.