OBJECTIVES: First-line treatment of aRCC has evolved from tyrosine kinase inhibitor (TKI) monotherapy in recent years, following approvals of immuno-oncology (IO) combination therapies. Dual IO combination (nivolumab+ipilimumab [NIVO+IPI]) and IO+TKI therapies (pembrolizumab+axitinib [PEMBRO+AXI] and nivolumab+cabozantinib [NIVO+CABO]) have demonstrated clinical benefit over sunitinib and are now recommended in international treatment guidelines. Pazopanib showed non-inferiority to sunitinib. This study assessed the cost-effectiveness of 1L aRCC treatments for an intention-to-treat population utilized in France from an all-payer perspective.

METHODS: A three-state partitioned survival model (progression-free disease, progressed disease, and death) was developed with a one-week cycle length and a 15-year time horizon. The model used patient characteristics and utilities (EQ-5D-3L) from the CheckMate 9ER trial (NCT03141177). Health state-specific utilities were calculated using the French value set. Multi-dimensional treatment effect network meta-analyses (NMAs) were used to estimate time-varying relative treatment effects on progression-free survival and overall survival relative to the anchor treatment sunitinib. All costs (€; cost year: 2020) were French-specific; costs and effects were discounted by 2.5% annually. Outcomes of interest were total costs, quality-adjusted life-years (QALYs), life-years (LYs), and the incremental cost-utility ratio (ICUR). Univariate deterministic analysis (DSA) assessed robustness of the results.

RESULTS: The cost-efficiency frontier was only comprised of two treatments: pazopanib and NIVO+IPI. The ICUR for NIVO+IPI vs. pazopanib was estimated at €219,344/QALY. NIVO+IPI was associated with the highest LYs (5.69) and QALYs (3.59). NIVO+IPI strictly dominated PEMBRO+AXI (∆€/∆QALY: 10,507/-0.428) and NIVO+CABO (∆€/∆QALY: 63,792/-0.221), and pazopanib strictly dominated sunitinib (∆€/∆QALY 21,333/-0.116). Among parameters tested in the DSA, key ICUR drivers were the estimates from the multi-dimensional treatment effect NMAs. Results were insensitive to modification of the structuring choices.

CONCLUSIONS: Over a 15-year time horizon, NIVO+IPI resulted in the highest survival and QALY gains among all 1L treatments and resulted in lower costs compared with PEMBRO+AXI or NIVO+CABO.