Abstract

To assess cost-effectiveness of pembrolizumab with carboplatin and paclitaxel (pembrolizumab combination) versus carboplatin plus paclitaxel (chemotherapy) or pembrolizumab monotherapy (in PDL1 ≥50% expressors) in previously untreated metastatic squamous non-small cell lung cancer (NSCLC). A three-state partitioned survival model was developed with a 30-year time horizon. The KEYNOTE-407(data cut off: April, 2018) trial informed the efficacy and adverse event parameters of pembrolizumab combination and chemotherapy. Overall survival (OS) was extrapolated using a piece-wise approach, utilising trial Kaplan-Meier data until week 52, and extrapolating overall survival beyond the trial using mortality risks for the chemotherapy group derived from an external real-world database (SEER) for the remainder of the time horizon, with a relative risk applied for pembrolizumab combination based on within-trial treatment efficacy. An indirect treatment comparison provided comparative effectiveness estimates of pembrolizumab combination versus pembrolizumab in PDL1 ≥50% expressors. Quality-adjusted life years (QALYs) were estimated using utilities derived from trial EQ-5D data. Resource use and unit costs were applied from an NHS perspective. The model demonstrated that pembrolizumab combination increases the life expectancy of patients from 1.76 to 3.29 discounted years, and from 1.27 to 2.42 discounted QALYs relative to chemotherapy use. The base case incremental cost-effectiveness ratio (ICER) versus paclitaxel plus carboplatin is £33,075, with a dominant result observed versus pembrolizumab monotherapy in PDL1 ≥50% expressors. The latter result should be interpreted with caution, as the hazard ratio for mortality is not statistically different between comparators and incremental QALYs are close to zero. Model results are most sensitive to assumptions around the extrapolation of overall survival data. The results of this cost-effectiveness analysis demonstrated that pembrolizumab combination is a cost-effective choice compared to standard of care therapies in the UK when considering a willingness to pay threshold of £50,000 per QALY, as per NICE end-of-life criteria.

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