Metastatic spread from breast cancer is the second-leading cause of brain metastasis (BM). Preclinical and clinical evidence suggests that abemaciclib, a selective CDK4/6 inhibitor, has the ability to cross the blood-brain barrier. To assess the intracranial objective response rate (iORR) of abemaciclib in patients with breast cancer with CNS involvement, Tolaney and colleagues performed a phase 2 clinical trial of abemaciclib with or without endocrine therap. or trastuzumab. Although this study did not meet its primary endpoint, abemaciclib was associated with an intracranial clinical benefit rate of 24% in patients with HR+, HER2- disease with secondary BM. Pharmacologically relevant evidence of abemaciclib was observed in BM and CSF from treated patients. Furthermore, in patients with leptomeningeal metastases, abemaciclib treatment led to disease control and improved OS longer than expected, based on historical controls. These results suggest the need for further study of abemaciclib in breast cancer with CNS metastasis, especially...

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