OBJECTIVES: The phase 3 KEYNOTE-177 trial demonstrated that first-line (1L) treatment with pembrolizumab significantly improved progression-free survival versus standard of care (SoC, 5-fluorouracil-based therapy with or without bevacizumab or cetuximab) in patients with MSI-H/dMMR stage IV CRC. This study re-evaluates the cost-effectiveness of pembrolizumab versus SoC and other 1L therapies from the United States (US) healthcare system perspective based on the 5-year follow-up data from KEYNOTE-177.

METHODS: Using 5-year follow-up clinical data for subsequent therapies, progression-free and overall survival from KEYNOTE-177, a three health state partitioned survival model was built to evaluate costs (2020 US Dollars; $) and outcomes with the use of pembrolizumab and SoC. Network meta-analysis was used to compare pembrolizumab with other therapies. Costs and health outcomes were discounted using an annual rate of 3%. Scenario analyses were performed which included an alternative state-transition model (STM) structure using trial-based post-progression survival data and a societal perspective.

RESULTS: Over a 40-year time horizon, pembrolizumab was cost-saving versus SoC, with an incremental quality-adjusted life-year (QALY) gain of 1.93, and reduction in costs of $15,843. The sensitivity analyses results were robust. Using an STM structure in scenario analyses resulted in a gain of 2.27 QALYs and additional cost of $18,147 for pembrolizumab leading to an incremental cost-effectiveness ratio (ICER) of $7,991 versus SoC. A societal perspective resulted in additional cost-savings from productivity gains due to delayed progression and death. Based on the previous analysis using second interim analysis data, the incremental QALYs were 1.61 and the incremental costs were $11,270, which resulted in an ICER of $6,984.

CONCLUSIONS: These analyses demonstrate that pembrolizumab remains a highly cost-effective 1L treatment option for patients with MSI-H/dMMR CRC. Results were comparable with previously published cost-effectiveness estimates while additional 5-year follow-up data help to address uncertainty in long-term survival outcomes.