On March 3, 2023, abemaciclib was approved for use with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of patients with hormone receptor (HR)-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.¹ Abemaciclib was previously approved in October 2021 for this population with the additional requirement of having a Ki67 score of at least 20%. The current approval removes the Ki67 testing requirement.

Supporting Efficacy Data

Approval was primarily based on findings in cohort 1 of the monarchE trial (ClinicalTrials.gov identifier NCT03155997). In cohort 1, 5,120 patients with high-risk disease—defined as either at least four pathologic axillary lymph nodes or one to three pathologic axillary lymph nodes with tumor grade 3 or size ≥ 50 mm—were randomly assigned to 2 years of abemaciclib plus physician’s choice of standard endocrine therapy (tamoxifen or an aromatase inhibitor; n = 2,555) or standard endocrine therapy alone (n = 2,565). To be enrolled in cohort 2, patients could not be eligible for cohort 1 and must have had one to three pathologic axillary lymph nodes and a tumor Ki67 score of at least 20%; in cohort 2, 253 patients were randomly assigned to abemaciclib plus endocrine therapy and 264, to endocrine therapy alone.

Abemaciclib plus endocrine therapy was associated with significantly better invasive disease–free survival vs endocrine therapy alone in the intent-to-treat population, largely attributable to outcomes in cohort 1. In cohort 1, invasive disease–free survival events occurred in 12.4% vs 18.5% of patients (hazard ratio = 0.653, 95% confidence interval [CI] = 0.567–0.753). Invasive disease–free survival at 48 months was 85.5% (95% CI = 83.8%–87.0%) vs 78.6% (95% CI = 76.7%–80.4%). Overall survival data were not mature; in cohort 2, death occurred in 10 patients given abemaciclib plus endocrine therapy vs 5 given endocrine therapy alone.

How It Is Used

The recommended abemaciclib starting dose is 150 mg taken twice daily with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity.

Product labeling provides instructions on dosage modification for adverse events including hematologic toxicities, diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, and venous thromboembolic events; concomitant use with ketoconazole and other strong or moderate CYP3A inhibitors (eg, clarithromycin, erythromycin, diltiazem); and severe hepatic impairment.

Safety Profile

Among the entire 5,591 patients in monarchE, the most common adverse events of any grade in the abemaciclib group were diarrhea (84% vs 9% in control group), infections (51% vs 39%), fatigue (41% vs 18%), nausea (30% vs 9%), and headache (20% vs 15%). The most common grade 3 or 4 adverse events included diarrhea (8% vs < 1%) and infections (6% vs 3%). The most common grade 3 or 4 laboratory abnormalities were leukopenia (19% vs 1%) and neutropenia (19% vs 2%).

Adverse events led to permanent discontinuation of abemaciclib in 19% of patients, most commonly because of diarrhea (5%) and fatigue (2%). Fatal adverse events occurred in 0.8% of the abemaciclib group, including cardiac failure, cardiac arrest, myocardial infarction, ventricular fibrillation, cerebral hemorrhage, cerebrovascular accident, pneumonitis, hypoxia, diarrhea, and mesenteric artery thrombosis.

Abemaciclib has warnings/precautions for diarrhea, neutropenia, interstitial lung disease/pneumonitis, hepatotoxicity, venous thromboembolism, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving abemaciclib. 

REFERENCE

1. Verzenio (abemaciclib) tablets prescribing information, Eli Lilly and Company, March 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208716s010s011lbl.pdf. Accessed March 13, 2023.