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. Endocrine therapy is a key treatment approach for early or metastatic HR+, HER2– breast cancer. The goal of treatment in early breast cancer is to prevent cancer recurrence, while therapy for metastatic breast cancer aims to slow or prevent cancer spread. Over the last 10 years, targeted therapy with CDK4/6 inhibitors has become an important component of cancer therapy for HR+, HER2– disease, usually used in combination with endocrine therapy to help patients reach these goals. One of the CDK4/6 inhibitors, abemaciclib, has shown the ability to improve survival outcomes for patients whether they have early or metastatic breast cancer. For patients with node-positive, high-risk early breast cancer, abemaciclib and endocrine therapy can help patients to stay cancer-free and live longer. For patients with metastatic breast cancer, abemaciclib combined with endocrine therapy has been shown to slow cancer spread and prolong survival. This paper outlines the main clinical trials that have shown how abemaciclib can add benefit to endocrine therapy in patients with HR+, HER2– breast cancer.