OBJECTIVES : To describe cost-effectiveness of pembrolizumab plus platinum-pemetrexed chemotherapies for first-line treatment of metastatic non-squamous non-small cell lung cancer (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-189, a phase-III randomized controlled trial comparing pembrolizumab+platinum-pemetrexed vs. platinum-pemetrexed alone in patients with metastatic non-squamous NSCLC with no EGFR/ALK mutations (cut-off date: November 8, 2017). A network meta-analysis was performed to consider other comparators used in French practice. Progression-free survival and overall survival estimates from the trial were extrapolated over a 10-year time horizon using a piecewise modelling approach based on parametric functions. QoL data were converted to French population-based utility values using a published algorithm. Only direct medical costs were considered, based on public sources. Costs and health outcomes were discounted at 4% per year. Incremental cost-effectiveness ratio (ICER) was calculated as cost per quality-adjusted life year (QALY) gained. Sensitivity and scenarios analyses were performed to assess robustness of results.

RESULTS : Overall, pembrolizumab+platinum-pemetrexed was projected to increase discounted life expectancy by 0.94 to 1.36 LYs per patient according to the specific comparator, corresponding to a gain of 0.66 to 0.95 QALYs per patient (an approximate doubling for both endpoints). This was associated with incremental costs per patient varying from +€33,021 to +€88,226. Then, the ICER of pembrolizumab+platinum-pemetrexed was estimated at €97,159/QALY vs. platinum-pemetrexed alone. Results were most sensitive to extrapolations of survival outcomes. However, later-published follow-up data reasonably validated projections. The willingness-to-pay (WTP) threshold should reach €120,000/QALY to have more than 80% probability of being cost-effective.

CONCLUSIONS : Combining pembrolizumab with platinum-pemetrexed doublet substantially improves life expectancy and appears cost-effective vs. using platinum-pemetrexed alone for first-line treatment of metastatic non-squamous NSCLC in France, assuming a WTP under €120,000/QALY.