On March 3, the U.S. Food and Drug Administration (FDA) approved abemaciclib (Verzenio) plus endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer at high risk of recurrence. Patients defined as high risk included those having either four or more pathologic axillary lymph nodes or one to three pathologic axillary lymph nodes and either a grade 3 tumor or a tumor ≥ 50 mm. Abemaciclib was previously approved for the above high-risk population with the additional requirement of having a Ki67 score of ≥ 20%; the new approval removes the Ki67 testing requirement.
monarchE
Efficacy was evaluated in monarchE (ClinicalTrials.gov identifier NCT03155997), a randomized (1:1), open-label, two-cohort multicenter trial including adult women and men with HR-positive, HER2-negative, node-positive, resected early breast cancer with clinical and pathological features consistent with a high risk of recurrence. To be enrolled in cohort 1, patients must have either four or more pathologic axillary lymph nodes or one to three pathologic axillary lymph nodes and either a grade 3 tumor or a tumor size ≥ 50 mm. To be enrolled in cohort 2, patients could not be eligible for cohort 1 and must have had one to three pathologic axillary lymph nodes and a tumor Ki67 score ≥ 20%. Patients were randomly assigned to receive either 2 years of abemaciclib plus physician’s choice of standard endocrine therapy (tamoxifen or an aromatase inhibitor) or standard endocrine therapy alone.
The major efficacy outcome measure was invasive disease–free survival. A statistically significant difference was observed in the intent-to-treat population, primarily attributed to the patients in cohort 1 (cohort 1 n = 5,120 [91%]; invasive disease–free survival hazard ratio = 0.653, 95% confidence interval [CI] = 0.567–0.753). Invasive disease–free survival at 48 months was 85.5% (95% CI = 83.8%–87.0%) for abemaciclib plus standard endocrine therapy and 78.6% (95% CI = 76.7%–80.4%) for standard endocrine therapy alone.
Overall survival data remain immature; however, in cohort 2, more deaths were observed with abemaciclib plus standard endocrine therapy compared to standard endocrine therapy alone (10 of 253 vs 5 of 264). Therefore, the indication was restricted to cohort 1.
The most commonly reported adverse reactions (occurring in ≥ 20% of patients) were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.
The recommended abemaciclib starting dose is 150 mg taken twice daily with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date. This application was also granted Priority Review.
