Pembrolizumab vs. chemotherapy in the first-line setting of PD-L1 ≥ 50% metastatic non-small cell lung cancer: a real-world cost-effectiveness analysis.

backgroundThe initial health technology assessments (HTA) for first-line pembrolizumab in PD-L1≥50% metastatic non-small cell lung cancer (mNSCLC) concluded that pembrolizumab could not be considered cost-effective based on clinical trial findings. We evaluated the real-world cost-effectiveness of first-line pembrolizumab versus platinum-based chemotherapy for PD-L1≥50% mNSCLC patients.

methodsWe retrospectively identified a population-based cohort of mNSCLC patients who received first-line pembrolizumab or platinum-based chemotherapy between April 2013 and March 2021, in Ontario, Canada. Propensity-score matching (1:1) was performed to balance covariates between the groups. Employing a public payer's perspective, all costs (CAD) and outcomes were estimated over a 4-year time horizon, adjusted for censoring and discounted at 1.5% yearly. Primary outcomes were life-years gained (LYG), quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER). To examine the sensitivity of the ICER to drug acquisition costs and discounting, we conducted a price reduction analysis and a scenario analysis of different discount rates.

resultsPropensity-score matching resulted in a total of 1,142 pairs of mNSCLC patients. Pembrolizumab extended survival with an incremental effect of 0.37 LYG and 0.35 QALY, but at an incremental cost of $56,681; the resulting ICERs were $154,941/LYG and $163,039/QALY. Though the ICERs were not sensitive to discounting rate, pembrolizumab price reductions of 31% and 55% were required to achieve cost-effectiveness at cost-effectiveness thresholds of $100,000/QALY and $50,000/QALY, respectively.

conclusionIn the real world, first-line pembrolizumab improves survival, but is not considered to be cost-effective for PD-L1≥50% mNSCLC. Improvements in cost-effectiveness, however, may be achievable through price renegotiations for pembrolizumab. KEY POINTS: This real-world cost-effectiveness analysis shows that pembrolizumab is not considered to be cost-effective compared to platinum-based chemotherapy in the real world, and that survival benefit was lower than observed in the initial trial. Notably, a price reduction analysis revealed that cost-effectiveness could be attained under conventional willingness-to-pay thresholds through 31-55% reductions to current list prices.