Real-World Evidence of Multi-Gene Panel Sequencing Effectiveness and Cost-Effectiveness for Advanced Cancers: A Tumor-Agnostic Target Trial Emulation

OBJECTIVES: Multi-gene panel sequencing streamlines the identification of therapeutic targets for personalized patient care. Adoption remains limited due to uncertain clinical and economic impacts. Evidence from randomized clinical trials (RCTs) is the standard for regulatory and reimbursement deliberations, yet is unavailable for many precision oncology interventions. We determined the effectiveness and cost-effectiveness of tumour-agnostic multi-gene panel sequencing compared to single-gene testing for advanced cancers, including advanced non-small cell lung cancer, melanoma, and colorectal cancer.

METHODS: Our population-based retrospective study followed the target trial emulation framework using patient-level linked administrative health databases. We considered adult British Columbia, Canada residents with an advanced cancer diagnosis who received multi-gene panel sequencing or single-gene EGFR/BRAF/KRAS tests between 2016-2018, emulating random assignment via genetic algorithm-based 1:1 matching. Our primary analysis included the same number of multi-gene panel patients and controls by tumour type. Our secondary analyses consider tumour-agnostic matching and stratified matching by tumour to understand the implications of tumour-specific versus tumour-agnostic evaluative frameworks. After 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 $50,000/LYG using inverse probability of censoring weighted linear regression and nonparametric bootstrapping.

RESULTS: We matched 1,176 patients receiving multi-gene panel sequencing to single-gene controls, achieving good balance on all 21 covariates. Incremental costs in the primary analysis were $6,263 (95%CI: $43, $13,326) and incremental LYG were 0.16 (95%CI: 0.06, 0.24). The INMB at $50,000/LYG was $1,653 (95%CI: -$4,350, $7,010), with a 72.0% probability of being cost-effective. Findings were not sensitive to the evaluative framework based on secondary analyses.

CONCLUSIONS: Implementation of a tumour-agnostic multi-gene panel for advanced cancers is likely cost-effective for health systems. This real-world evidence can inform best practices for tumour-agnostic evaluations and support policymakers in reimbursement deliberations for precision oncology interventions.