The Food and Drug Administration (FDA) has approved Verzenio® (abemaciclib), in combination with endocrine therapy (tamoxifen or an aromatase inhibitor), for the adjuvant treatment of adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of at least 20%, as determined by an FDA-approved test.
The approval was based on data from the randomized, open-label, 2 cohort, multicenter phase 3 monarchE trial (ClinicalTrials.gov Identifier: NCT03155997), which evaluated the efficacy and safety of abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6, in adult women and men with HR+, HER2-, node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of disease recurrence. Patients were randomly assigned 1:1 to receive 2 years of abemaciclib 150mg twice daily plus physician’s choice of standard endocrine therapy or standard endocrine therapy alone.
The primary end point was invasive disease-free survival (IDFS), defined as the time from randomization to the first occurrence of 1 of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary nonbreast invasive cancer, or death attributable to any cause.
Among 2003 patients with a Ki-67 score of at least 20%, prespecified analysis showed a statistically significant improvement in IDFS with abemaciclib plus endocrine therapy compared with endocrine therapy alone (104 events [10.2%] vs 158 events [16%], respectively; hazard ratio, 0.626; 95% CI, 0.488-0.803; P =.0042). The absolute IDFS benefit rate at 3 years was 7.1%. At the time of IDFS analysis, overall survival data were immature.
As for safety, the most common adverse reactions (incidence of 10% or greater) in the abemaciclib plus endocrine therapy arm, and at least 2% higher than the endocrine therapy arm alone, were diarrhea, infections, fatigue, nausea, headache, vomiting, stomatitis, decreased appetite, dizziness, rash, and alopecia.
“The design and results of the monarchE study are practice-changing and represent the first advancement in adjuvant treatment of HR+ HER2- breast cancer in a very long time,” said Sara M. Tolaney, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute, and investigator on the monarchE study. “This FDA approval for Verzenio in combination with endocrine therapy in the early breast cancer setting has the potential to become a new standard of care for this population.”
- FDA approves Verzenio® (abemaciclib) as the first and only CDK4/6 inhibitor for certain people with HR+ HER2- high risk early breast cancer. News release. Eli Lilly and Company. Accessed October 13, 2021. https://www.prnewswire.com/news-releases/fda-approves-verzenio-abemaciclib-as-the-first-and-only-cdk46-inhibitor-for-certain-people-with-hr-her2–high-risk-early-breast-cancer-301398910.html.
- Verzenio. Package insert. Eli Lilly and Company; 2021. Accessed October 13, 2021. https://pi.lilly.com/us/verzenio-uspi.pdf.