The FDA has approved abemaciclib (Verzenio®, Eli Lilly and Company) in combination with endocrine therapy consisting of an aromatase inhibitor or tamoxifen as adjuvant therapy for patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-positive early breast cancer with a high risk of recurrence. Abemaciclib, the first CDK4/6 inhibitor to be approved in the adjuvant breast cancer setting, is indicated for patients with a Ki-67 score of ≥20%. In addition, the FDA has approved the Ki-67 IHC MIB-1 pharmDx (Dako OmnisTM, Agilent) assay as a companion diagnostic to determine eligibility for treatment with abemaciclib.
"Although many patients with HR-positive, HER2-negative disease will not experience recurrence or have distant recurrence with standard therapies alone, up to 20% of patients may experience disease recurrence in the first 10 years, often with distant metastases, at which time the disease is uncurable," wrote Stephen Johnston, MD, PhD, Head of Medical Oncology at the Royal Marsden National Health Services (NHS) Foundation Trust in London, and colleagues, in their publication of results of the monarchE trial (NCT03155997), on which the approval was based."It is therefore critical to optimize adjuvant therapy to prevent early recurrences and metastases for these patients."
The phase 3 trial enrolled 5,637 female and male patients with high-risk, HR-positive, HER2-negative, node-positive early breast cancer, who had undergone surgery and had received radiotherapy and/or adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 150 mg abemaciclib twice daily in combination with physician's choice of standard endocrine therapy, or standard endocrine therapy alone, for two years. The primary end point was invasive disease–free survival, with secondary end points of distant relapse–free survival, overall survival, and safety.
Among 2,003 patients who had a Ki-67 score of ≥20% and a high risk of recurrence, abemaciclib produced a statistically significant improvement in invasive disease–free survival (P=0.0042), with 36-month invasive disease–free survival rates of 86.1% for abemaciclib plus tamoxifen or an aromatase inhibitor versus 79.0% for those receiving tamoxifen or an aromatase inhibitor alone. At the time of analysis, overall survival data had not yet been reached.
Adverse events occurring in at least 20% of patients receiving abemaciclib plus endocrine therapy included diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.
"Abemaciclib when combined with endocrine therapy is the first CDK4/6 inhibitor to demonstrate a significant improvement in invasive disease–free survival in patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of early recurrence," concluded Dr. Johnston and colleagues in their December 2020 publication in the Journal of Clinical Oncology.
The recommended starting dose of abemaciclib is 150 mg taken twice daily in combination with either tamoxifen or an aromatase inhibitor, for two years or until disease recurrence or unacceptable toxicity.
For More Information
Johnston SRD, Harbeck N, Hegg R, et al (2020). Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2–, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol, 38(34):3987-3998. DOI:10.1200/JCO.20.02514
US Food & Drug Administration (2021). FDA approves abemaciclib with endocrine therapy for early breast cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-abemaciclib-endocrine-therapy-early-breast-cancer
Image credit: National Cancer Institute