Cost-effectiveness analysis of pembrolizumab versus standard-of-care chemotherapy for first-line treatment of PD-L1 positive (>50%) metastatic squamous and non-squamous non-small cell lung cancer in France

Introduction: In 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.

Methods: A 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.

Results: For 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.

Conclusions: Pembrolizumab 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).