On October 12, 2021, the FDA approved the combination of abemaciclib (Verzenio; Eli Lilly) plus endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adults with hormone receptor (HR)-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score ≥20%, as determined by an FDA-approved test. Abemaciclib is the first CDK4/6 inhibitor to receive FDA approval for adjuvant treatment of breast cancer.
On the same day, the FDA also approved the Ki-67 IHC MIB-1 pharmDx (Dako Omnis) assay as a companion diagnostic test for selecting appropriate patients for this combination therapy.
This approval was based on the monarchE study, a randomized, open-label, 2-cohort multicenter clinical trial. The study included women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer and clinical and pathological features consistent with a high risk for disease recurrence. Patients were randomized in a 1 to 1 ratio to 2 years of abemaciclib plus their physician’s choice of endocrine therapy or to endocrine therapy alone.
The primary end point was invasive disease-free survival (IDFS). In the 2003 patients with high risk for disease recurrence and Ki-67 score ≥20%, the use of abemaciclib plus endocrine therapy showed significant improvement in IDFS (hazard ratio, 0.626; 95% confidence interval [CI], 0.488-0.803; P = .0042) versus endocrine therapy alone. At 36 months, the IDFS was 86.1% (95% CI, 82.8-88.8) with abemaciclib plus endocrine therapy compared with 79.0% (95% CI, 75.3-82.3) with endocrine therapy alone. The overall survival data were not mature at the time of the analysis.
The most common (≥20%) side effects were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.