The potential survival gain and cost-effectiveness of circulating tumor DNA-guided treatment switching in advanced...

Circulating tumor DNA (ctDNA) has emerged as a minimally invasive approach to assess treatment response in cancer. While ctDNA response has been associated with greater survival outcomes, the clinical benefit and economic value of using ctDNA to inform early treatment switching is unclear. The objective was to estimate the potential effectiveness and cost-effectiveness of ctDNA-guided treatment switching in advanced NSCLC.

We developed a semi-Markov model to estimate survival gains in weeks, incremental quality-adjusted life years (QALYs), incremental costs, and incremental cost-effectiveness ratios with ctDNA-guided treatment switching relative to standard of care (SOC). The model used survival parameters from the Prospective Clinico-Genomic study. We evaluated ctDNA testing at 6, 10, or 15 weeks post-treatment initiation, assuming varying degrees of improved efficacy with the subsequent treatment regimen with earlier switching (odds ratios 0.7-1.0).

In the base-case scenario, assuming 10-week testing with 10% mortality reduction, ctDNA-guided switching yielded 4.0 weeks survival gain (95% uncertainty interval: -2.5, 10.9) at an additional cost of $3975 ($3,755, $4179), resulting in an incremental cost-effectiveness ratio of $87,941 per QALY. These findings suggest a 66% probability that ctDNA-guided therapy would be cost-effective at $150,000 per QALY. Earlier testing and stronger efficacy assumptions improved estimates, with survival gains ranging from 2.0 to 7.4 weeks across scenarios.

ctDNA-guided treatment switching may provide modest survival benefits within accepted cost-effectiveness thresholds, though substantial uncertainty exists. The magnitude of clinical benefit and economic value depends on the timing of ctDNA assessment and the efficacy advantage conferred by earlier treatment switching.