OBJECTIVES: Despite curative-intent surgery, some early-stage NSCLC patients experience recurrence and ultimately succumb to cancer. The CheckMate-816 phase 3 randomized trial demonstrated that neoadjuvant nivolumab plus PDC reduces the risk of progression or death versus neoadjuvant PDC. Nivolumab is used in France via an early access program for stage II-IIIA NSCLC tumors expressing PD-L1≥1%. This study evaluates its cost-effectiveness compared to neoadjuvant PDC alone from the French healthcare perspective.

METHODS: A semi-Markov model with four health-states (event-free, locoregional-recurrence, distant-recurrence, and death) compared neoadjuvant nivolumab plus PDC to PDC alone. The CheckMate-816 study results in PD-L1≥1% and intention-to-treat populations informed time-to-recurrence, pre- and post-recurrence survivals, subsequent treatments, and French utilities based on the EQ-5D-3L questionnaire. Costs were based on a study from French hospital claims database. Base case analysis had a 20-year time horizon to limit long term uncertainty, with a 2.5% annual cost and outcome discount. Uncertainty was assessed through sensitivity analyses.

RESULTS: Neoadjuvant nivolumab plus PDC resulted in a QALY gain of 1.37 (+23%) and cost savings of €4,167 (-8%) compared to neoadjuvant PDC. Alternative assumptions on time horizon, survival extrapolations, treatment effect waning, costs, and utilities had limited impact on results and were unlikely to modify the conclusions on the dominance of neoadjuvant nivolumab plus PDC over PDC alone. Only one scenario assuming equivalent subsequent treatment distribution for both arms yielded a non-dominant result with a €1,542/QALY incremental cost-effectiveness ratio. Probabilistic sensitivity analyses confirmed deterministic results with a 76% probability of dominance for nivolumab plus PDC.

CONCLUSIONS: Neoadjuvant nivolumab plus PDC for resectable NSCLC is the first oncology treatment to be validated by the French National Health Authority (HAS) as both cheaper and more effective compared to alternatives. This outcome is attributed to reduced progression risk associated with relatively high utility scores, delayed or avoided subsequent treatments and nivolumab short treatment duration