On March 3, 2023, the US FDA approved abemaciclib (Verzenio, Eli Lilly and Company) for adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer in patients who have a high risk* of recurrence.^1,2 Abemaciclib should be given with endocrine therapy (ET) consisting of tamoxifen or an aromatase inhibitor. This change from the original approval removes the requirement for Ki-67 proliferation index testing in this population.

Abemaciclib is a CDK4/6 inhibitor and may cause interstitial lung disease (ILD) or pneumonitis. In early breast cancer patients in the monarchE trial, 3% had ILD or pneumonitis of any grade, 0.4% had grade 3 or 4 reactions, and 1 fatality occurred (0.1%). Monitor patients for hypoxia, cough, or trouble breathing. Other possible severe adverse effects include diarrhea, neutropenia, hepatotoxicity, or venous thromboembolism. Abemaciclib should not be used during pregnancy or breastfeeding, and women should use birth control during treatment and for at least 3 weeks after the last dose. The most common adverse reactions, occurring in more than 20% of patients, are diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.

The recommended starting dose in early breast cancer is 150 mg orally twice daily (with tamoxifen or an aromatase inhibitor) for 2 years or until disease recurrence or unacceptable toxicity.

This expanded approval is based on the results obtained in the phase 3 randomized, open-label monarchE trial of women and men with HR-positive, HER2-negative, node-positive early breast cancer. Specifically, the results of the 5120 patients in cohort 1, all of whom met the definition of high-risk,* were used. A significant improvement in invasive disease-free survival (IDFS) was found at 2 years with the use of abemaciclib plus standard ET (tamoxifen or an aromatase inhibitor), compared with ET alone. The increase was even greater at 4 years. IDFS at 48 months was 85.5% in patients given abemaciclib plus ET, versus 78.6% with ET alone. The use of abemaciclib plus ET resulted in a 35% relative reduction in the risk of recurrence, compared with ET alone (hazard ratio [HR], 0.653 [95% CI, 0.567-0.753]).

In an additional analysis of 2056 patients who had received neoadjuvant chemotherapy, abemaciclib plus ET lead to clinically meaningful benefits in IDFS and in distant relapse-free survival (DRFS), compared with ET treatment alone.³ The observed absolute improvement was 6.6% in 2-year IDFS and 6.7% in 2-year DRFS.

*High risk is defined as ≥4 pathologic axillary lymph nodes (pALN) OR 1 to 3 pALN and a tumor that is either ≥50 mm or grade 3.

References

1. Verzenio (abemaciclib). Prescribing information. Lilly USA, LLC; 03/2023. Accessed March 14, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208716s010s011lbl.pdf
2. US Food and Drug Administration. FDA expands early breast cancer indication for abemaciclib with endocrine therapy. Updated March 3, 2023. Accessed March 7, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-early-breast-cancer-indication-abemaciclib-endocrine-therapy
3. Martin M, Hegg R, Kim S-B, et al. Treatment with adjuvant abemaciclib plus endocrine therapy in patients with high-risk early breast cancer who received neoadjuvant chemotherapy: a prespecified analysis of the monarchE randomized clinical trial. JAMA Oncol. 2022;8(8):1190-1194. doi:10.1001/jamaoncol.2022.1488