On March 3, 2023, 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, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer who are at high risk for recurrence.

FDA Expands Early Breast Cancer Indication for Abemaciclib With Endocrine Therapy

Patients are defined as high risk if they have either at least four pathologic axillary lymph nodes (pALNs) or one to three pALNs and either tumor grade 3 or a tumor size of at least 50 mm.

Abemaciclib was previously approved for the same high-risk population, but a Ki-67 score of at least 20% was also required. The new approval removes the testing requirement.

Efficacy was evaluated in monarchE (NCT03155997), a randomized (1:1), open-label, two-cohort multicenter 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 at least four pALNs or patients with one to three pALNs and either tumor grade 3 or a tumor size of at least 50 mm. Cohort 2 consisted of patients not eligible for cohort 1 who had one to three pALNs and tumor Ki-67 score of at least 20%. Patients were randomized to either two years of abemaciclib plus their healthcare provider’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 the patients in cohort 1 (cohort 1 n = 5,120 [91%]; IDFS HR = 0.653 [95% CI = 0.567, 0.753]). IDFS 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 remains immature; however, in cohort 2, more deaths were observed with abemaciclib plus standard endocrine therapy compared to standard endocrine therapy alone (10/253 versus 5/264). Therefore, the indication is restricted to patients who meet the critera for cohort 1.

The most common adverse reactions experienced in at least 20% of patients treated with abemaciclib were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.

Abemaciclib’s recommended starting dose is 150 mg taken twice daily with tamoxifen or an aromatase inhibitor until patients complete two years of treatment or until they experience disease recurrence or unacceptable toxicity.

View the full prescribing information for abemaciclib.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. FDA approved this application two months ahead of the FDA goal date.

The application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.