OBJECTIVES: Multi-gene panel sequencing streamlines treatment selection for advanced non-small cell lung cancer (NSCLC). Implementation continues to be uneven across jurisdictions, in part due to uncertain clinical and economic impacts compared to single-gene testing. 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 patients receiving multi-gene panel sequencing with contemporaneous controls receiving single-gene testing, maximizing balance on observed 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. Our probabilistic analysis used nonparametric bootstrapping with 1000 replications to account for estimation uncertainty.

RESULTS: We matched 858 panel-eligible advanced NSCLC patients to controls, achieving balance for the 16 included covariates. Average 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 $3,529(95%CI:-$4,268,$10,942) and mean incremental LYG were 0.08(95%CI:-0.04,0.18). Among the 1,000 bootstrap samples, 14.5% had lower costs and increased survival and 78.6% had higher costs and increased survival. The probability of multi-gene panel sequencing being cost-effective was 57.5% at $50,000/LYG and 84.0% at $100,000/LYG(INMB:$4,575[95%CI:-$5,468,$14,064]).

CONCLUSIONS: Implementation of panel-based sequencing has been slow compared to the rapid development of new targeted therapies. Using population-based real-world data, we found a relatively high probability that panel-based testing to inform targeted treatment for NSCLC would be cost-effective at conventional thresholds.