MECHANISM OF ACTION — CDKs 4 and 6 regulate the G1/S phase transition within the cell cycle; they are often overexpressed in HR-positive breast cancer, leading to cell cycle progression and cell proliferation. Inhibition of CDK 4/6 results in cell cycle arrest, senescence, and apoptosis.

CLINICAL STUDIES — FDA approval of abemaciclib for the new indication was based on the results of an open-label trial (monarchE) in 5637 women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer at high risk of recurrence (≥4 positive pathologic axillary lymph nodes or 1-3 positive axillary lymph nodes and at least one of the following: tumor size ≥5 cm, histologic grade 3, or Ki-67 score ≥20%). Patients were randomized to receive abemaciclib 150 mg twice daily for 2 years plus investigator-selected endocrine therapy or endocrine therapy alone for up to 10 years. At a median of 42 months, median invasive disease-free survival (IDFS) was not reached in either group. At 4 years, IDFS with abemaciclib plus endocrine therapy was 85.8% compared to 79.4% with endocrine therapy alone.4

ADVERSE EFFECTS — Abemaciclib can cause diarrhea, neutropenia, fatigue, leukopenia, nausea, anemia, and headache. In the monarchE trial, there were two treatment-related deaths in the abemaciclib plus endocrine therapy group and none in the endocrine therapy alone group.

DOSAGE, ADMINISTRATION, AND COST — The recommended starting dosage of abemaciclib for the new indication is 150 mg taken twice daily in combination with tamoxifen or an aromatase inhibitor. The drug should be taken for a total of 2 years or until disease recurrence or unacceptable toxicity occurs. A 30-day supply of Verzenio costs $15,571.80.5