OBJECTIVES: Compared to single-gene BRAF testing to guide targeted treatment for advanced melanoma, multi-gene panels can identify additional gene mutations with known therapeutic or prognostic relevance. No randomized control trials of multi-gene panel sequencing have been completed in advanced melanoma. This study determined the cost-effectiveness of multi-gene panel sequencing compared to single-gene BRAF testing for advanced melanoma.

METHODS: Our population-based retrospective study emulated a hypothetical pragmatic trial using comprehensive patient-level clinical and health administrative data between September 2016 and December 2018 from British Columbia, Canada. To emulate random treatment assignment, we 1:1 matched multi-gene panel patients to contemporaneous controls using a machine learning approach that maximized balance on 15 clinical and sociodemographic characteristics. Following matching, we estimated mean three-year survival time and costs (2021 CAD), and calculated incremental net monetary benefit (INMB) for life-years gained (LYG) at $100,000/LYG using inverse probability of censoring weighted linear regression and nonparametric bootstrapping. Besides an intention-to-treat (ITT) effect, we also estimated the per-protocol (PP) effect of initiating treatment within 90 days of receiving test results additionally using inverse probability of treatment weights.

RESULTS: We matched 147 patients receiving multi-gene panel sequencing to controls, achieving good balance for all included covariates. ITT mean incremental costs were $19,541 (95%CI:-$18,939,$77,396;P=0.41) and mean incremental LYG were 0.22 (95%CI:-0.06,0.50;P=0.12). PP incremental costs and LYG were $36,367 (95%CI:-$6,653,$120,216;P=0.22) and 0.56 (95%CI:0.39,1.24;P<0.01), respectively. The probability of multi-gene panel sequencing being cost-effective at $100,000/LYG was 55% in the ITT analysis and 65% in the PP analysis.

CONCLUSIONS: We found the cost-effectiveness of multi-gene panel sequencing compared to single-gene BRAF testing to be evenly poised, with estimates favouring multi-gene panel sequencing with respect to overall survival and cost-effectiveness when accounting for probability of treatment initiation. This real-world evidence generated using randomized trial design principles can support jurisdictions’ deliberations on the reimbursement of precision oncology interventions.