A Cost-Effectiveness Analysis of First-Line Therapies for Microsatellite-Instability-High (MSI-H) or Mismatch-Repair-Deficient (dMMR) Unresectable or Metastatic Colorectal Cancer (mCRC) in France
Author(s)
Paul Casabianca, PharmD1, Romain Cohen, MD2, Antoine Georges, PharmD3, Linde Pronk, MSc4, Nicholas Durno, MSc5, Romane Gerrer-Soustiel, MSc1, Christophe Jamain, PhD1, FRANCOIS-EMERY COTTE, PhD1, Kiran Dave, MSc6, Sebastien Branchoux, PhD1.
1Bristol Myers Squibb, Rueil Malmaison, France, 2Hôpital Saint-Antoine, Paris, France, 3Vyoo Agency, Paris, France, 4Open Health, Amersfoort, Netherlands, 5Open Health, Leamington Spa, United Kingdom, 6Bristol Myers Squibb, Welwyn Garden City, United Kingdom.
1Bristol Myers Squibb, Rueil Malmaison, France, 2Hôpital Saint-Antoine, Paris, France, 3Vyoo Agency, Paris, France, 4Open Health, Amersfoort, Netherlands, 5Open Health, Leamington Spa, United Kingdom, 6Bristol Myers Squibb, Welwyn Garden City, United Kingdom.
OBJECTIVES: The current standard treatment for patients with dMMR/MSI-H mCRC in France is pembrolizumab, which demonstrated superiority over chemotherapy±targeted therapy (CT) in the KeyNote-177 trial. Recently, the CheckMate-8HW trial demonstrated significant reduction of the risk of progression or death of nivolumab+ipilimumab (N+I) compared with CT. Aligned with the French HTA body guidelines, this study assesses the cost-effectiveness of these first-line systemic therapies from a healthcare system perspective.
METHODS: A three-state (progression-free, progressed-disease, and death) semi-Markov model comparing N+I with pembrolizumab, and CT, was developed. Costs (€2024, French-specific) and health outcomes were discounted by 2.5% annually over a 15-year time horizon. The model's only treatment-dependent transition probability was time-to-progression, defined through an indirect treatment comparison (fractional polynomials) using CheckMate-8HW and KeyNote-177 results. Utilities per health-state were derived from CheckMate-8HW EQ-5D-3L questionnaires using a mixed model for repeated measures and adjusting for clinically relevant and statistically significant variables. Uncertainty was assessed through deterministic (DSA) and probabilistic (PSA) sensitivity analysis. One scenario analysis was pairwise comparison of N+I to pembrolizumab as it is the standard of care in France.
RESULTS: N+I achieved 5.7 quality-adjusted life years (QALY) for a total cost of €106,518, pembrolizumab achieved 4.1 QALY at €105,037, and CT resulted in 2.9 QALY for €35,010. Pembrolizumab was extendedly dominated: its incremental cost-utility ratio (ICUR) versus CT was twice as high as N+I’s (€25,439/QALY versus CT). DSA showed modest uncertainty with all ICUR below €29,021/QALY. PSA illustrated that pembrolizumab was extendedly dominated in 49% of cases, strictly dominated by N+I in 47% of cases (less QALY and higher costs), and that 80% of N+I simulations fell below €29,700/QALY versus CT. The pairwise scenario analysis indicated a €964/QALY ICUR for N+I versus pembrolizumab.
CONCLUSIONS: Despite a dual therapy acquisition cost and advanced oncology setting, N+I provides a favorable ICUR driven by high efficacy in an immunotherapy-sensitive population.
METHODS: A three-state (progression-free, progressed-disease, and death) semi-Markov model comparing N+I with pembrolizumab, and CT, was developed. Costs (€2024, French-specific) and health outcomes were discounted by 2.5% annually over a 15-year time horizon. The model's only treatment-dependent transition probability was time-to-progression, defined through an indirect treatment comparison (fractional polynomials) using CheckMate-8HW and KeyNote-177 results. Utilities per health-state were derived from CheckMate-8HW EQ-5D-3L questionnaires using a mixed model for repeated measures and adjusting for clinically relevant and statistically significant variables. Uncertainty was assessed through deterministic (DSA) and probabilistic (PSA) sensitivity analysis. One scenario analysis was pairwise comparison of N+I to pembrolizumab as it is the standard of care in France.
RESULTS: N+I achieved 5.7 quality-adjusted life years (QALY) for a total cost of €106,518, pembrolizumab achieved 4.1 QALY at €105,037, and CT resulted in 2.9 QALY for €35,010. Pembrolizumab was extendedly dominated: its incremental cost-utility ratio (ICUR) versus CT was twice as high as N+I’s (€25,439/QALY versus CT). DSA showed modest uncertainty with all ICUR below €29,021/QALY. PSA illustrated that pembrolizumab was extendedly dominated in 49% of cases, strictly dominated by N+I in 47% of cases (less QALY and higher costs), and that 80% of N+I simulations fell below €29,700/QALY versus CT. The pairwise scenario analysis indicated a €964/QALY ICUR for N+I versus pembrolizumab.
CONCLUSIONS: Despite a dual therapy acquisition cost and advanced oncology setting, N+I provides a favorable ICUR driven by high efficacy in an immunotherapy-sensitive population.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EE10
Topic
Economic Evaluation
Topic Subcategory
Trial-Based Economic Evaluation
Disease
Oncology