Practical Guidance on Abemaciclib in Combination with Adjuvant Endocrine Therapy for Treating Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative High-Risk Early Breast Cancer.

The most common subtype of breast cancer is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, accounting for 65-70% of all breast cancer cases diagnosed in the United States. Until 2015, single-agent endocrine therapy (ET) was the recommended first-line treatment for metastatic HR-positive, HER2-negative breast cancer. However, the paradigm has since shifted, as targeted therapy is now recommended in combination with ET. The cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment of this breast cancer subtype, and combining either palbociclib, ribociclib, or abemaciclib with ET is now the standard first-line treatment for metastatic disease. Results of clinical trials in the metastatic setting have demonstrated that treatment with the combination of a CDK4/6 inhibitor and ET rather than ET alone is associated with longer overall survival, longer progression-free survival, and better objective response rates. Each of the CDK4/6 inhibitors has been investigated in combination with ET in patients with early-stage HR-positive, HER2-negative breast cancer who are at high risk of relapse. In October 2021, abemaciclib was the first CDK4/6 inhibitor approved in combination with ET by the US Food and Drug Administration for adjuvant treatment of patients with HR-positive, HER2-negative, high-risk early breast cancer. Herein, we provide practical guidance on the use of abemaciclib in combination with ET for HR-positive, HER2-negative, high-risk early breast cancer to assist clinicians in their day-to-day practice, and we review clinically relevant topics of dosing, side effect management, sequencing and optimal timing for initiation, and patient selection.