A phase 2 study of abemaciclib in patients with brain metastases secondary to non-small cell lung cancer or melanoma

Background: Abemaciclib is a selective cyclin-dependent kinase 4 and 6 inhibitor that penetrates the blood-brain barrier, resulting in comparable concentrations in tissue and plasma. The primary objective of this nonrandomized Simon two-stage phase II trial (NCT02308020) was to evaluate the intracranial objective response rate in patients with brain metastases secondary to breast cancer (already published), non-small cell lung cancer (NSCLC), or -melanoma receiving abemaciclib. Secondary objectives evaluated safety, extracranial response, progression-free survival (PFS), and overall survival (OS). Methods: Eligible subjects were enrolled in NSCLC or melanoma tumor-specific cohorts and treated with abemaciclib 200 mg twice daily (BID) monotherapy or 150 mg BID for NSCLC patients on concurrent pemetrexed or gemcitabine. Results: 23). No confirmed intracranial response was observed in either cohort. Volumetric decrease in target intracranial lesions was 22.7% for NSCLC and 18.8% for melanoma cohorts. Intracranial clinical benefit rate was 26.1% (95% CI: 8.1-44) for NSCLC and 9.1% (95% CI: 0-21.1) for melanoma cohorts. In the NSCLC cohort, median OS and PFS were 7.1 months (95% CI: 3.7-9.4) and 1.6 months (95% CI: 1.4-3.5), respectively. In the melanoma cohort, median OS and PFS were 2.9 months (95% CI: 1.2-4.3) and 1.4 months (95% CI: 1.0-2.0), respectively. Abemaciclib safety was consistent with previously reported data. Conclusions: Although abemaciclib can achieve therapeutic concentrations in brain metastases tissue, this study did not meet its primary endpoint. The limited clinical activity in this study suggests that further clinical trials should focus on the use of abemaciclib combination therapy.