On March 3, 2023, the FDA approved abemaciclib (Verzenio; Eli Lilly) plus 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 at high risk for recurrence. Patients defined as high risk included those having either ≥4 pathologic axillary lymph nodes (pALNs) or 1 to 3 pALNs and either a grade 3 tumor or a tumor size of ≥50 mm. Abemaciclib was previously approved for the same high-risk population with the added requirement of having a Ki67 score ≥20%; the new approval removes this testing requirement.
Efficacy was assessed in monarchE, a randomized, open-label, 2-cohort, multicenter clinical trial including adult patients with HR-positive, HER2-negative, node-positive, resected, early breast cancer with clinical and pathologic features consistent with a high risk for recurrence. Cohort 1 consisted of patients with ≥4 pALNs or patients with 1 to 3 pALNs and either a grade 3 tumor or a tumor size of ≥50 mm. Cohort 2 consisted of patients not eligible for cohort 1 who had 1 to 3 pALNs and a tumor Ki67 score of ≥20%. Patients were randomized 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 (IDFS). A statistically significant difference was observed in the intent-to-treat population, primarily attributed to cohort 1 (N = 5120 [91%]; IDFS hazard ratio, 0.653; 95% confidence interval [CI], 0.567-0.753). IDFS at 48 months was 85.5% (95% CI, 83.8-87.0) for abemaciclib plus endocrine therapy and 78.6% (95% CI, 76.7-80.4) for endocrine therapy alone. Overall survival data remain immature; however, in cohort 2, more deaths were observed with abemaciclib plus endocrine therapy compared with endocrine therapy alone. Therefore, the indication is restricted to patients who meet the criteria for cohort 1.
“Our goal in intensifying treatment for early breast cancer is to maintain remission and prevent the recurrence of cancer. The magnitude of benefit seen in the four-year data from the monarchE study reinforces my confidence in adjuvant Verzenio as the standard-of-care for high-risk patients in this setting,” said Erika P. Hamilton, MD, Medical Oncologist and Director, Breast and Gynecological Research, Sarah Cannon Research Institute, Brentwood, TN, and an investigator on the monarchE trial. “The initial Verzenio FDA approval in early breast cancer was practice-changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them.”
The most common (≥20%) adverse reactions were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.