Repotrectinib was effective for carcinomatous meningitis occurring during the treatment of early-generation ROS1 TKIs for ROS1 fusion-positive NSCLC: A case report

Crizotinib and entrectinib, which are early-generation ROS1 tyrosine kinase inhibitors (TKIs), are the standard treatments for unresectable ROS1 fusion-positive non-small cell lung cancer (NSCLC). However, insufficient efficacy in the central nervous system (CNS) and acquired resistance remain important clinical challenges. Repotrectinib, a next-generation ROS1 TKI with potent activity against CNS metastasis and acquired resistance, is expected to overcome these problems. We report the case of a 47-year-old woman with ROS1 fusion-positive NSCLC who developed carcinomatous meningitis during entrectinib treatment. Repotrectinib, the third ROS1 TKI, resulted in marked clinical improvement against carcinomatous meningitis. However, the patient also experienced bilateral limb muscle weakness during the administration of repotrectinib and diffuse myalgia after discontinuation of repotrectinib. This time course raised the possibility of the direct adverse effect and withdrawal phenomena related to the treatment. This case highlights the significant therapeutic potential of repotrectinib for CNS metastases, and the importance of careful management of withdrawal symptoms.