The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On March 3, 2023, the Food and Drug Administration (FDA) approved abemaciclib (Verzenio, Eli Lilly and Company) 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 at high risk of recurrence.

Patients defined as high risk included those having either ≥4 pALN (pathologic axillary lymph nodes) or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm.

Abemaciclib was previously approved for the above high-risk population with the additional requirement of having a Ki-67 score ≥20%. Today’s approval removes the Ki-67 testing requirement. 

View full prescribing information for Verzenio. 

Efficacy was evaluated in monarchE (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 ≥4 pALN or 1-3 pALN and either tumor grade 3 or a tumor size ≥50 mm. To be enrolled in cohort 2, patients could not be eligible for cohort 1 and must have had 1-3 pALN and tumor Ki-67 score ≥20%. Patients were randomized to 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 (ITT) population, primarily attributed to the patients in cohort 1 (cohort 1 N=5120 [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 vs. 5/264). Therefore, the indication was restricted to cohort 1. 

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 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 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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

For information on the COVID-19 pandemic, see the following resources:

• FDA: Coronavirus Disease 2019 (COVID-19)
• NCI: Coronavirus: What People With Cancer Should Know
• CDC: Coronavirus (COVID-19)

Follow the Oncology Center of Excellence on Twitter @FDAOncology. 

Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.