On October 12, 2021, abemaciclib was approved for use with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of adults with hormone receptor–positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki67 score ≥ 20%, as determined by an FDA approved test.1 Abemaciclib is the first cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor approved for adjuvant treatment of breast cancer. The FDA also approved the Ki67 IHC MIB-1 pharmDx assay as a companion diagnostic for selecting patients for this indication.
Supporting Efficacy Data
Approval was supported by the open-label phase III monarchE trial (ClinicalTrials.gov identifier NCT03155997), in which 5,591 patients were randomly assigned to physician choice of tamoxifen or aromatase inhibitor endocrine therapy with (n = 2,791) or without (n = 2,800) abemaciclib at 150 mg twice daily for 2 years. The primary analysis included 1,107 patients who received abemaciclib and 986 control patients with a Ki67 score ≥ 20%.
Invasive-disease survival at 36 months was 86.1% (95% confidence interval [CI] = 82.8%–88.8%) in the abemaciclib group vs 79.0% (95% CI = 75.3%–82.3%) in the control group (hazard ratio [HR] = 0.626, 95% CI = 0.488–0.803, P = .0042). Overall survival data were not mature at the time of this analysis.
How It Is Used
The recommended abemaciclib starting dose is 150 mg twice daily in combination with tamoxifen or an aromatase inhibitor until 2 years or disease recurrence or unacceptable toxicity. In severe hepatic impairment, the dose should be reduced to 150 mg once daily.
Product labeling provides instructions on dosage modification for adverse events including hematologic toxicities, diarrhea, hepatotoxicity, interstitial lung disease/pneumonitis, venous thromboembolic events, persistent or recurrent grade 2 toxicities, and grade 3 or 4 toxicity; as well as for concomitant use with ketoconazole and other strong or moderate CYP3A inhibitors and strong or moderate CYP3A inducers.
Among the entire 5,591 patients in monarchE, the most common adverse events of any grade (≥ 20%) in the abemaciclib group were diarrhea (84% vs 9% in the 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 due to 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.
1. Verzenio (abemaciclib) tablets prescribing information, Eli Lilly and Company, October 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf. Accessed November 18, 2021.