Abstract
Abstract Background Abemaciclib is a selective CDK4 & 6 inhibitor approved to treat patients (pts) with HR+, HER2- advanced breast cancer (ABC) on a continuous dosing schedule as monotherapy or in combination with endocrine therapy.1,2,3 Clinical data demonstrate that abemaciclib can penetrate the blood brain barrier resulting in comparable abemaciclib concentrations in brain metastases tissues, cerebrospinal fluid, and plasma.4 We report safety and efficacy results of abemaciclib in pts with leptomeningeal metastases (LM) arising from HR+, HER2- ABC. Methods Study I3Y-MC-JPBO (NCT02308020) is a multicenter, open-label, Phase 2 trial evaluating the safety and efficacy of abemaciclib in 6 cohorts of pts with brain metastases secondary to HR+ ABC, non-small cell lung cancer, or melanoma. Here we discuss a subgroup of cohort F: pts with HR+, HER2- LM from ABC, documented by positive CSF cytology or by clinical signs and symptoms associated with abnormal MRI features. Pts with concomitant parenchymal brain metastases were allowed, but must have been stable for ≥4 weeks following wholebrain radiotherapy or stereotactic radiosurgery. Abemaciclib was orally administered 200mg twice daily on a 21-day cycle.The key exploratory objectives were to assess the effect of abemaciclib on pts with LM secondary to HR+, HER2- ABC based on safety and tolerability, and radiological assessment from the Response Assessment in Neuro-Oncology leptomeningeal metastases (RANO-LM) criteria. Results Between December 2015 and July 2016, 17 pts were enrolled in cohort F. This study reports on the 7 pts with HR+, HER2- ABC LM of which 4 pts were diagnosed with concurrent parenchymal brain metastases. Median duration of treatment was 3.9 months (range, 0.9-10.6), with 3 pts remaining on treatment for more than 6 months. Pts discontinued treatment due to progressive disease (PD, n=5) and adverse events (n=2). Median overall survival (OS) was 8.4 months (range, 3.3-14.2). Best investigator-assessed overall response was stable disease (SD) in 5 pts and progressive disease (PD) in 2 pts. Efficacy, as per CNS imaging, revealed SD in 4 pts (no imaging, n=1), 2 of which had stable or improved symptoms per neurological assessment response. Best overall intracranial response of parenchymal metastases was 1 complete response, 1 SD, and 2 PD. All 4 pts with extracranial disease had best overall response of SD. All pts experienced ≥1 TEAE, with the most common grade 3 TEAEs including nausea (28.6%), pain (28.6%), and vomiting (28.6%); 1 pt (14.3%) experienced grade 4 anemia and grade 4 upper gastrointestinal hemorrhage. Conclusion OS for pts with LM arising from HR+, HER2- ABC is typically 4 months or less despite available therapies5. Here we report the median OS within this subgroup as 8.4 months. Concurrent intracranial and extracranial disease control was observed. Safety and tolerability results are similar to those previously reported with abemaciclib. Further study of abemaciclib in a larger pt cohort is warranted.
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