IntroductionIn the KEYNOTE-024 trial, pembrolizumab demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) versus Standard-of-Care (SoC) platinum-based doublets for first-line treatment of PD-L1 -positive (≥50%) metastatic Non-Small-Cell Lung Cancer (NSCLC) patients with no EGFR mutations or ALK translocations. This study aims to assess the cost-effectiveness of pembrolizumab versus SoC platinum-based chemotherapy from the French healthcare system perspective. MethodsA three-state partitioned-survival model was adapted to project outcomes and costs of squamous and non-squamous NSCLC patients respectively, over a 10-year time horizon. Clinical and utility data were collected from the trial. A network meta-analysis was performed to consider platinum-based triplets also used for non-squamous NSCLC. Direct medical costs were considered based on ressources identified from the trial and literature. Costs and outcomes were discounted at 4% per year. Incremental cost-effectiveness ratios (ICERs) were calculated as cost per Life Year (LY) and cost per Quality-Adjusted Life Year (QALY). Sensitivity and scenario analyses were performed to assess the robustness of results. ResultsFor squamous NSCLC, pembrolizumab was projected to increase life expectancy of patients by 0.93 LY (11 months), and 0.74 QALY (9 months) for an incremental cost of €62,032 compared with platinum-based doublets. The ICER of pembrolizumab versus platinum-based doublets was €66,825/LY and €84,097/QALY. For non-squamous NSCLC, pembrolizumab was projected to increase life expectancy of patients by 0.85–1.32 LYs (10.2–15.8 months) and 0.64–1.02 QALYs (7.7–12.2 months) for an incremental cost varying from €-14,947-+47,064 depending on the specific comparator. The ICER of pembrolizumab versus platinum-based chemotherapy with paclitaxel plus bevacizumab was €62,846/LY and €78,729/QALY; regimens including pemetrexed were dominated. Results were most sensitive to extrapolations of survival outcomes and assumptions for continued effectiveness and treatment duration of pembrolizumab. ConclusionsPembrolizumab appears cost-effective versus SoC chemotherapy for first-line treatment of PD-L1-positive (50%) metastatic NSCLC patients in France, assuming willingness-to-pay under 100,000€/QALY (OECD threshold in the discussion section).