Abemaciclib in HR+, HER2- Breast Cancer: A Narrative Review of the Clinical Evidence

Hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) breast cancer comprises approximately 70% of all breast cancer cases. In early-stage breast cancer, adjuvant endocrine therapy (ET) reduces recurrence and mortality, while in advanced/metastatic breast cancer (MBC), ET prolongs survival and delays the use of chemotherapy. However, there remains a need for agents that further improve outcomes across the spectrum of breast cancer presentations. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, ribociclib, and palbociclib, are used in combination with ET as a standard of care first-line option in HR+, HER2- advanced disease to improve survival outcomes. Moreover, the addition of abemaciclib and ribociclib to adjuvant ET reduces risk of cancer recurrence, with abemaciclib also improving overall survival. Here, we provide a comprehensive analysis of the clinical trials that have demonstrated the efficacy of abemaciclib across the HR+, HER2- breast cancer continuum, improving outcomes in both high-risk, node-positive early breast cancer as well as in advanced disease. Abemaciclib has also been shown to be effective when combined with a variety of ET options, including aromatase inhibitors, tamoxifen, fulvestrant, imlunestrant, or as monotherapy, and has shown efficacy regardless of prior CDK4/6 inhibitor exposure, ESR1 or PI3K pathway mutational status, menopausal status, and in both endocrine-sensitive and endocrine-resistant breast cancer. Importantly, the safety profile of abemaciclib has been consistent across trials and allows the administration of the drug over long periods of time when needed, particularly if dose-reduction strategies are employed. Together, the data summarized in this publication help inform clinical decision making regarding the role of abemaciclib in the treatment of patients with both early and metastatic HR+, HER2- breast cancer.