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Abemaciclib for the treatment of brain metastases (BM) secondary to hormone receptor positive (HR+), HER2 negative breast cancer.
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2017
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Breast OncologyBrain MetastasesOral Selective Cdk4PharmacotherapyPre-clinical PharmacologyNeuro-oncologyMetronomic TherapyClinical TrialsAnti-cancer AgentRadiation OncologyMolecular OncologyCancer ResearchHealth SciencesMedicineResponse RateCancer TreatmentPharmacologyEndocrine-related CancerImmune Checkpoint InhibitorBreast CancerOncologyAbemaciclib 200
1019 Background: Abemaciclib is an oral selective CDK4 and CDK6 inhibitor administered on a continuous dosing schedule, which has demonstrated clinical activity and an acceptable safety profile in patients (pts) with heavily pre-treated HR+ metastatic breast cancer (MBC). Abemaciclib has been shown preclinically to cross the blood-brain barrier, providing rationale for testing this agent in pts with BM. Furthermore, as previously presented, levels of abemaciclib similar to plasma were detected in resected BM in a subset of pts with HR+, HER2- MBC in this study. Methods: Study I3Y-MC-JPBO is an open-label, Phase 2, Simon 2-Stage trial evaluating the safety and efficacy of abemaciclib 200 mg BID in pts with new or progressive BM secondary to HR+ MBC, NSCLC, or melanoma. Eligible pts in Part B (the focus of this presentation) include pts with HR+, HER2- MBC who have ≥1 measurable brain lesion. The primary objective was objective intracranial (IC) response rate as defined by Response Assessment in Neuro-Oncology BM response criteria. Secondary objectives (IC related) include best overall response, duration of response, disease control rate, and clinical benefit rate. Exploratory objectives include assessment of drug concentrations in resected tumors. Safety, tolerability, and PK of abemaciclib were also assessed. Stage 1 includes 23 pts; if < 2 of the 23 pts respond to abemaciclib, futility is met. However, if ≥2 respond, 33 additional pts are to be enrolled to Stage 2. Results: This Stage 1 efficacy analysis included 23 pts; 32 pts were included in the safety analysis. Although 5 pts were considered nonevaluable, 2 pts (8.7%) had confirmed partial response (PR) (meeting the predefined threshold for advancement to Stage 2); enrollment is ongoing. At the time of the analysis, the 2 pts with PR had completed 14 and 15 cycles each (21d cycles) of therapy. The majority of adverse events were gastrointestinal in nature, consistent with previous studies of abemaciclib. Conclusions: This study has provided preliminary evidence that abemaciclib penetrated BM in pts with HR+, HER2- MBC and had antitumor activity in this population. Final results will be presented following Stage 2 analyses. Clinical trial information: NCT02308020.