Presentation (CTI)

OBJECTIVES: ROS1 fusions represent a rare subset of alterations affecting 1-2% of patients with advanced non-small cell lung cancer (NSCLC). Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) that demonstrated durable clinical activity in locally advanced or metastatic ROS1+ NSCLC in the non-randomized phase I/II TRIDENT-1 trial. Other TKIs, such as entrectinib, are approved for ROS1+ NSCLC. Evaluating costs relative to health benefits, such as progression-free survival (PFS), is essential for optimal resource allocation. The objective of this work was to assess the economic and clinical value of repotrectinib versus entrectinib in a TKI-naive population from a societal perspective.
METHODS: Cost per PFS-based responder was defined as the cost per PFS probability at 3 years. This interval reflects reported duration of response (DOR) for included treatments. Individual patient data from TRIDENT-1 informed clinical efficacy for repotrectinib (e.g. PFS, DOR, and overall survival [OS]), with entrectinib data estimated via a published matching-adjusted indirect comparison (MAIC). Parametric models were fitted to efficacy data for repotrectinib, and hazard ratios were used to estimate entrectinib curves. Costs included drug acquisition, medical expenses, adverse event management, and productivity loss. The number needed to treat to prevent a progression/death based on the restricted mean survival time (NNT_RMST) was also estimated.
RESULTS: At 3 years, PFS probabilities were 0.42 for repotrectinib and 0.22 for entrectinib. Costs per PFS-based responder were $2,108,603 for repotrectinib and $2,780,560 for entrectinib, with annualized costs of $702,868 and $926,853, respectively. The NNT_RMST was 4, indicating that treating four patients with repotrectinib would prevent one progression/death.
CONCLUSIONS: This study demonstrates the economic and clinical benefits of repotrectinib versus entrectinib in TKI-naive patients with ROS1+ NSCLC. Cost per PFS-based responder provides a pragmatic evaluation of the investment required to extend progression-free outcomes in ROS1+ NSCLC patients.