Abstract P1-17-03: Abemaciclib for the treatment of brain metastases secondary to hormone receptor positive breast cancer
Authors: Bachelot T , Kabos P , Yardley D , Dieras V , Costigan T , Klise S , Awada A 
Published: February 2018

Abstract
Background: Although a lower percentage of patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC) develop brain metastases when compared with triple negative and HER2+ MBC patients, there are no regulatory approved systemic agents for the treatment of HR+ breast cancer brain metasteses, and this remains an unmet medical need. Standard local treatment options include surgery, stereotactic radiosurgery (SRS), and/or whole brain radiation therapy (WBRT). Abemaciclib, an oral selective CDK4 and 6 inhibitor administered on a continuous dosing schedule, has demonstrated clinical activity and an acceptable safety profile in heavily pre-treated HR+ MBC patients. Preclinically, abemaciclib crosses the blood-brain barrier, which is further supported clinically by detectable levels of abemaciclib similar to plasma levels in resected brain metastases in a subset of patients with HR+, HER2- MBC as previously reported for the current study. Together these data provide further rationale for evaluating abemaciclib in patients with brain metastases.
Methods: Study I3Y-MC-JPBO (NCT02308020) is an open-label, Phase 2, Simon 2-Stage trial evaluating the safety and efficacy of abemaciclib up to 200 mg BID in 4 cohorts of patients with brain metastases secondary to HR+ MBC, NSCLC, or melanoma. With regard to HR+ MBC, one cohort included HR+, HER2- patients, another one included HR+/HER2+ patients. All HR+ MBC patients enrolled to 1 of these 2 cohorts were required to have at least 1 measurable brain lesion. The primary objective was objective intracranial response rate as defined by Response Assessment in Neuro-Oncology brain metastases response criteria. Stage 1 was to enroll 23 evaluable patients per study part; if ≥2 respond to abemaciclib, 33 additional evaluable patients were to be enrolled to Stage 2. Secondary CNS objectives include best overall response, duration of response, and clinical benefit rate.
Results: For Stage 1 efficacy, in patients with HR+, HER2+ MBC futility was met. However, for HR+, HER2- patients, 2 confirmed, durable partial responses were observed and enrollment to Stage 2 is ongoing.
Conclusions: Previously, this study provided evidence that abemaciclib penetrates brain metastases in patients with HR+, HER2- MBC. The current results provide sufficient evidence of anti-tumor activity on brain metastases in patients with HR+, HER2- MBC to merit further exploration, but not for patients with HR+, HER2+ disease. Safety and tolerability results are similar to those previously reported for abemaciclib, with the majority of adverse events being gastrointestinal.
Citation Format: Bachelot T, Kabos P, Yardley D, Dieras V, Costigan T, Klise S, Awada A. Abemaciclib for the treatment of brain metastases secondary to hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-03.