On October 12, 2021, the FDA approved a new indication for the cyclin-dependent kinase (CDK)4/6 inhibitor abemaciclib (Verzenio; Eli Lilly), in combination with tamoxifen or an aromatase inhibitor as initial endocrine-based therapy, for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, node-positive, early breast cancer at high risk for recurrence, and a Ki-67 score ≥20%, as determined by an FDA-approved test.
“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,” said Sara M. Tolaney, MD, MPH, Chief, Breast Oncology, and Associate Director, Susan F. Smith Center for Women’s Cancers, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, and an investigator on the monarchE study. “We are encouraged by the marked reduction in the risk of recurrence even beyond the 2-year treatment period in these patients, and I’m grateful to be able to offer this as a treatment option to my patients.”
This new indication is based on results of the monarchE trial, a randomized, open-label, multicenter study of adult women and men with HR-positive, HER2-negative, node-positive, resected early breast cancer with clinical and pathologic features consistent with a high risk for disease recurrence. Patients were randomized in a 1:1 ratio to receive 2 years of abemaciclib 150 mg twice daily plus physician’s choice of standard endocrine therapy, or standard endocrine therapy alone.
The main efficacy end point measure was invasive disease-free survival (iDFS). In patients with risk for recurrence and Ki-67 score ≥20%, results showed a statistically significant improvement in iDFS (hazard ratio, 0.62; 95% CI, 0.49-0.8; P = .0042). The iDFS at 36 months was 86.1% (95% CI, 82-88.8) for patients treated with abemaciclib plus endocrine therapy and 79% (95% CI, 75.3-82.3) for those treated with endocrine therapy alone. OS data were not mature at the time of the iDFS analysis.
The most common (≥20%) AEs were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.
The recommended abemaciclib starting dose is 150 mg twice daily in combination with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence or unacceptable toxicity.