FDA Approves Adjuvant Abemaciclib Plus ET for Resected High-Risk Early Breast Cancer


Based on a subgroup analysis from the monarchE trial, the FDA approved abemaciclib as adjuvant therapy in women with high-risk early breast cancer

The FDA approved abemaciclib (Verzenio) plus endocrine therapy (ET) as adjuvant treatment for patients with hormone receptor (HR)–positive, HER2-negative, node-positive early breast cancer who are at high risk of recurrence and have a Ki-67 score of 20% or greater, according to the drug’s developer, Eli Lilly and Company.

Determination of K9-67, a marker of cellular proliferation, is to be determined by an FDA-approved test.

“The design and results of the monarchE study are practice-changing and represent the first advancement in adjuvant treatment of [HR-positive, HER2-negative] breast cancer in a very long time,” Sara M. Tolaney, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute, and investigator on the monarchE study, said in a statement. “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. 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.”

Results of the open-label, multicenter phase 3 monarchE trial (NCT03155997) support the FDA’s decision. Patients with HR-positive, HER2-negative resected early breast cancer and with clinical and pathological features associated with a high-risk of disease recurrence were randomized in a 1:1 fashion to receive 2 years of abemaciclib 150 mg twice per day plus ET or ET alone, with adjuvant ET continuing for up to 10 years as recommended by their treating clinician.

Abemaciclib resulted in an improvement in the primary end point of invasive disease-free survival (iDFS), defined as time it takes for disease to recur, versus ET alone at a pre-specified interim analysis. In a pre-specified analysis in patients with high-risk disease (n = 2003), a statistically significant improvement in iDFS was observed with abemaciclib/ET vs ET alone, equating to a 37% reduced risk of breast cancer recurrence or death (HR, 0.643; 95% CI, 0.475-0.872; P = .0042). The absolute iDFS benefit rate at 3 years was 7.1%.

Patients in the pre-specified analysis were those with high-risk clinical and pathological factors such as a Ki-67 score of 20% or higher, 4 or more positive axillary lymph nodes, and 1 to 3 positive axillary lymph nodes with either grade 3 disease or tumors greater than 5 cm. This indication is based upon the results in this subgroup and additional follow-up done post-hoc.

Adverse events noted in more than 10% of patients with the experimental combination in monarchE were diarrhea, infections, fatigue, nausea, headache, vomiting, stomatitis, decreased appetite, dizziness, rash, and alopecia. Laboratory abnormalities occurring in more than 10% of patients included creatinine increased, white blood cell count decreased, neutrophil count decreased, anemia, lymphocyte count decreased, platelet count decreased, alanine aminotransferase increased, aspartate aminotransferase increased, and hypokalemia.

“Over time, the collective results of the Verzenio clinical development program have demonstrated a differentiated CDK4/6 inhibitor profile, and the landmark data from the monarchE trial that supported this new indication in [HR-positive, HER2-negative] early breast cancer represent another important step forward for people who are in need of new treatment options,” Jacob Van Naarden, senior vice president, CEO of Loxo Oncology at Lilly and president, Lilly Oncology, said in a statement. “We are pleased with this initial approval in the adjuvant setting and as these data continue to mature, we look forward to further opportunities to work with health authorities to expand the use of Verzenio in this setting.”

More data from the trial are schedule for presentation at the 2021 European Society for Medical Oncology Congress Virtual Plenary Session.


FDA Approves Verzenio (abemaciclib) as the First and Only CDK4/6 Inhibitor for Certain People with HR+ HER2- High Risk Early Breast Cancer. Eli Lilly and Company. News release. October 13, 2021. Accessed October 13, 2021. https://bit.ly/3DFt5I7

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