A phase II study of abemaciclib in patients (pts) with brain metastases (BM) secondary to HR+, HER2- metastatic breast cancer (MBC).

1017 Background: Abemaciclib is a selective CDK4 & 6 inhibitor approved to treat HR+, HER2- MBC pts on a continuous dosing schedule as monotherapy or in combination with endocrine therapy (ET). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting in comparable concentrations in tissues and plasma. Methods: JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt cohorts with BM secondary to HR+ MBC, non-small cell lung cancer, or melanoma. Here, we report on HR+, HER2- MBC pts. Eligible pts had ≥1 new or not previously irradiated measurable BM ≥10mm or a progressive previously irradiated BM. Pts receiving ET at the time of enrollment were permitted to continue the same ET provided that extracranial (EC) disease was stable ≥3 months and the CNS progression occurred on the ET. Abemaciclib was orally administered 200mg BID. Primary endpoint was objective intracranial response rate (OIRR; [CR+PR]) based on Neuro-Oncology BM response assessment criteria (RANO-BM). Secondary endpoints included intracranial clinical benefit rate, PFS, and safety. Results: 58 HR+, HER2- MBC pts were enrolled and 52 pts were evaluable. Pts had a median of 4 prior systemic therapies, 75% of pts had prior chemotherapies (0-6, median of 2), and 71% of pts had prior ET (0-4, median of 1), in the metastatic setting. 50% of pts had prior whole brain radiotherapy, 39% stereotactic radiosurgery, and 8% surgical resection of BM. Median time from radiation to study enrollment was 9.4 months. Out of the 52 evaluable patients, 3 pts had a confirmed intracranial response (6% OIRR), and 38% of pts showed a decrease in the sum of their intracranial target lesions. Intracranial clinical benefit rate (CR+PR+SD persisting for ≥ 6 months) was 25%. Median PFS was 4.4 months (95% CI, 2.6-5.5). Safety and tolerability were similar to previous reports for abemaciclib. Conclusions: Abemaciclib demonstrated intracranial clinical benefit in heavily pretreated HR+, HER2- MBC pts with BM in this study. Further evaluations are ongoing to identify ABC patients with BM who might benefit most from abemaciclib. Clinical trial information: NCT02308020.