Real-world cost-effectiveness of multi-gene panel sequencing to inform therapeutic decisions for advanced non-small cell lung cancer: a population-based study

Background: Multi-gene panel sequencing streamlines treatment selection for advanced non-small cell lung cancer (NSCLC). Implementation continues to be uneven across jurisdictions, partly due to uncertain clinical and economic impacts. In British Columbia (BC), Canada, the public healthcare system reimbursed a multi-gene panel in September 2016. This study determined the population-level cost-effectiveness of publicly reimbursed multi-gene panel sequencing compared to single-gene testing for advanced NSCLC. Methods: Our population-based retrospective study design used patient-level linked administrative health databases. We considered adult BC residents with a panel-eligible lung cancer diagnosis between September 2016 and December 2018. Using a machine learning approach, we conducted 1: 1 genetic algorithm matching of recipients receiving multi-gene panel sequencing to controls receiving single-gene testing, maximising balance on observed demographic and clinical characteristics. Following matching, we estimated mean three-year survival time and costs (public healthcare payer perspective; 2021 CAD) and calculated the incremental net monetary benefit (INMB) for life-years gained (LYG) at conventional willingness-to-pay thresholds using inverse probability of censoring weighted linear regression and nonparametric bootstrapping. Findings: We matched 858 panel-eligible advanced NSCLC patients to controls, achieving balance for the 16 included covariates. Average test turnaround times were 18. 6 days for multi-gene panel sequencing and 7. 0 days for single-gene testing. After matching, mean incremental costs were 3529 (95% CI: -4268, 10, 942) and mean incremental LYG were 0. 08 (95% CI: -0. 04, 0. 18). Among the 1000 bootstrap samples, 14. 5% had lower costs and increased survival and 78. 6% had higher costs and increased survival. The INMB was 523 (95% CI: -6256, 7023) at 50, 000/LYG, with a 57. 5% probability of being cost-effective, and 4575 (95% CI: -5468, 14, 064) at 100, 000/LYG, with an 84. 0% probability of being cost-effective. Interpretation: Using population-based real-world data, we found a moderate to high probability that panel-based testing to inform targeted treatment for NSCLC would be cost-effective at higher thresholds. Funding: This research was supported by Genome British Columbia/Genome Canada (G05CHS) and the Terry Fox Research Institute.