OBJECTIVES : To describe the cost-effectiveness of pembrolizumab in combination with carboplatin + paclitaxel/nab-paclitaxel for first-line treatment of metastatic squamous NSCLC, from the French healthcare system perspective.

METHODS : A previously published partitioned-survival model was adapted to fit with French HTA guidelines for economic evaluation. Clinical and quality of life (QoL) data were derived from KEYNOTE-407, a phase-III randomized controlled trial comparing pembrolizumab+carboplatin+paclitaxel/nab-paclitaxel vs. carboplatin+paclitaxel/nab-paclitaxel alone in patients with metastatic squamous NSCLC (cut-off date: April 3, 2018). An indirect treatment comparison was performed to consider pembrolizumab as monotherapy in high-expressing tumors (PD-L1≥50%). Progression-free survival and overall survival (OS) estimates from the trial were extrapolated over a 10-year time horizon using a piecewise modelling approach based on parametric functions. EQ-5D QoL data were converted to French population-based utility values using a published algorithm. Only direct medical costs were considered, based on public sources (incl. list price). Costs and health outcomes were discounted at 4% per year. Incremental cost-effectiveness ratios (ICER) were calculated as a cost per life-year (LY) or quality-adjusted life-year (QALY) gained. Sensitivity and scenarios analyses assessed robustness of results.

RESULTS : Per patient, pembrolizumab in combination was projected to increase discounted life expectancy by 0.59 LY and 0.46 QALY with an incremental cost of €53,292 compared with carboplatin+paclitaxel/nab-paclitaxel alone. ICERs were €90,669/LY and €116,606/QALY. Results were most sensitive to OS extrapolations, assumptions for continued effectiveness of pembrolizumab in combination and duration of subsequent treatment. Interpretation of results vs. pembrolizumab monotherapy in the PD-L1 ≥50% subgroup was limited due to a high degree of uncertainty in relative outcomes for OS. At a willingness-to-pay (WTP) threshold ≥ €165,000/QALY, pembrolizumab in combination has a ≥ 80% probability of being cost-effective.

CONCLUSIONS : Combining pembrolizumab with carboplatin+paclitaxel/nab-paclitaxel substantially improves life expectancy and appears cost-effective vs. carboplatin+paclitaxel/nab-paclitaxel alone for first-line treatment of metastatic squamous NSCLC in France, assuming a WTP under €165,000/QALY.