On October 12, the U.S. Food and Drug Administration (FDA) approved abemaciclib (Verzenio) in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, node-positive early breast cancer who are at high risk of disease recurrence and who also have a Ki67 score ≥ 20%, as determined by an FDA-approved test. This is the first CDK 4/6 inhibitor approved for the adjuvant treatment of breast cancer.
The FDA also approved the Ki67 IHC MIB-1 pharmDx (Dako Omnis) assay, submitted by Agilent, Inc, as a companion diagnostic for selecting patients for this indication.
Efficacy was evaluated in monarchE, a randomized (1:1), open-label, two-cohort multicenter trial that included adult women and men with HR-positive, HER2-negative, node-positive, resected early breast cancer with clinical and pathologic features consistent with a high risk of disease recurrence. Patients were randomly assigned to receive either 2 years of abemaciclib plus their physician’s choice of standard endocrine therapy or standard endocrine therapy alone.
The major efficacy outcome measure was invasive disease–free survival. In patients with a high risk of recurrence and Ki67 score ≥ 20% (n = 2,003), the trial demonstrated a statistically significant improvement in invasive disease–free survival (hazard ratio = 0.626, 95% confidence interval [CI] = 0.488–0.803, P = .0042). Invasive disease–free survival at 36 months was 86.1% (95% CI = 82.8–88.8) for patients receiving abemaciclib plus tamoxifen or an aromatase inhibitor and 79.0% (95% CI = 75.3–82.3) for those receiving tamoxifen or an aromatase inhibitor. Overall survival data were not mature at the time of the invasive disease–free survival analysis.
The most common adverse reactions (≥ 20%) were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.
The recommended abemaciclib starting dose is 150 mg taken twice daily in combination with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.