Abstract
Introduction: Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) are at increased risk of central nervous system (CNS) metastasis at initial diagnosis and throughout treatment. In a phase 3 trial, lorlatinib, a third-generation ALK tyrosine kinase inhibitor, significantly improved progression-free survival. In further analysis, lorlatinib revealed superior intracranial efficacy and prolonged time to intracranial progression compared with crizotinib. Case Presentation: Herein, we report a case of ALK-positive NSCLC with leptomeningeal metastasis that was successfully treated with lorlatinib after progression to brigatinib and alectinib. This case demonstrates the potential of lorlatinib in managing leptomeningeal metastasis in ALK-positive NSCLC. Conclusion: The case suggests a paradigm shift in therapeutic approaches for CNS metastasis, including brain and leptomeningeal metastases.