OBJECTIVES: To assess the cost-effectiveness of pembrolizumab vs. standard-of-care (SoC) treatments for first-line treatment in adult patients with microsatellite instability high (MSI-H)/mismatch repair-deficient (dMMR) unresectable or metastatic colorectal (mCRC) cancer in France.

METHODS: A three-state transition model (pre-progression, post-progression and death) was developed and adapted to the French setting in order to estimate health outcomes and costs of MSI-H/dMMR mCRC over a 15-year time horizon. Efficacy, safety and utility data were derived from phase III KEYNOTE-177 (KN-177) study (cut-off February 19^th 2020), which compared pembrolizumab to SoC (chemotherapy +/- targeted therapy). Progression-free survival (PFS), time to progression (TTP), post-progression survival (PPS), and time on treatment (ToT) from KN-177 study were extrapolated based on parametric methods. Costs included drug acquisition and administration of first and second-line treatment, transportation, follow-up, adverse events management, surgery and end of life. Costs and outcomes were discounted at 2.5% per year. Incremental cost-effectiveness ratio (ICER) was calculated and robustness of the results were assessed using deterministic and probabilistic sensitivity analyses and scenario analyses.

RESULTS: The estimated ICER of pembrolizumab vs. SoC treatments is €47,333/QALY and €44,385/LY (expected gain: 1.52 QALYs (18.2 months) and 1.62 LY (19.4 months); incremental cost: €71,753). Pembrolizumab had a 90% chance of being the most efficient strategy for a willingness-to-pay of €54,000/QALY. The deterministic sensitivity analysis showed that varying the input parameters within their 95% CI had a limited impact on the ICER (variations of less than 5%). The parameter with the greatest impact on the ICER was the estimated pre-progression utility for pembrolizumab. Scenario analyses having the greatest impact on the ICER used separate PPS curves per treatment arm with second-line treatment distribution from KN-177 (€21 480/QALY).

CONCLUSIONS: Pembrolizumab is cost-effective vs. SoC treatments for first-line treatment of adult patients with MSI-H/dMMR mCRC in France assuming a willingness-to-pay of €54,000/QALY.