Clinical Effectiveness and Cost-Effectiveness of Multigene Panel Sequencing in Advanced Melanoma: A Population-Level Real-World Target Trial Emulation.

Abstract

Targeted therapy and immunotherapy promise improved survival in patients with advanced melanoma, yet the effectiveness and cost-effectiveness of multigene panel sequencing compared with single-gene <i>BRAF</i> testing to guide therapeutic decisions is unknown. Our population-based quasi-experimental retrospective target trial emulation used comprehensive patient-level data for 364 British Columbia, Canada, adults with an advanced melanoma diagnosis receiving multigene panel sequencing or single-gene <i>BRAF</i> testing between September 1, 2016, and December 31, 2018. We 1:1 matched multigene panel patients to controls using genetic algorithm-based matching. Outcomes included 3-year overall survival (OS) and health care costs (2021 Canadian dollars [CAD]) with incremental net monetary benefit for life-years gained (LYG). Outcomes were analyzed using inverse probability of censoring weighted linear regression for the intention-to-treat (ITT) effect. The per-protocol (PP) effect estimation also included stabilized inverse probability of treatment weights. We then used Weibull regression and Kaplan-Meier survival analysis. We matched 147 multigene panel patients to controls, achieving balance for all covariates. After matching, ITT incremental costs were $19,447 CAD (95% CI, -$18,516 to $76,006) and incremental LYG were 0.22 (95% CI, -0.05 to 0.49). We found uncertainty in differences on OS using Kaplan-Meier (<i>P</i> = .11) and Weibull regression (hazard ratio [HR], 0.73 [95% CI, 0.51 to 1.03]) in the ITT. PP incremental costs were $36,367 CAD (95% CI, -$6,653 to $120,216]) and incremental LYG were 0.56 (95% CI, 0.39 to 1.24), with corresponding differences in OS using Kaplan-Meier (<i>P</i> = .02) and Weibull regression (HR, 0.56 [95% CI, 0.36 to 0.87]). The probability of multigene panels being cost-effective at $100,000/LYG CAD was 55% for ITT and 65% for PP. The cost-effectiveness of multigene panels was evenly poised at higher thresholds, even when accounting for treatment initiation. Health systems reimbursing multigene panels and expensive therapies may be confronted with a value tradeoff, in which there may be improved survival albeit with a modest change in cost-effectiveness.