FDA Approves Adjuvant Abemaciclib Plus ET for Select Patients With HR+/HER2-, Node-Positive Early Breast Cancer

The combination of abemaciclib and endocrine therapy has been approved by the FDA as an adjuvant treatment for a subgroup of patients with hormone receptor-positive, HER2-negative, node-positive, early breast cancer.

The FDA has granted approval to abemaciclib (Verzenio), in combination with endocrine therapy, for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 (a marker of cellular proliferation) score of ≥20% as determined by an FDA-approved test, according to a press release issued by Eli Lilly and Company.1

Approval of the abemaciclib combination for this indication was based on data from the phase 3 monarchE trial (NCT03155997), a randomized. open-label, 2-cohort, multicenter study of approximately 5637 patients.

"The design and results of the monarchE study are practice-changing and represent the first advancement in the adjuvant treatment of HR+, HER2- breast cancer in a very long time," said Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology, Susan F. Smith Center for Women's Cancers associate director, Susan F. Smith Center for Women's Cancers senior physician, and associate professor of Medicine, Harvard Medical School Dana-Farber Cancer Institute. “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 two-year treatment period in these patients, and I'm grateful to be able to offer this as a treatment option to my patients."

In monarchE, patients were randomized 1:1 to receive either oral abemaciclib 150 mg with endocrine therapy or endocrine therapy alone. The primary end point of the study was invasive disease-free survival (iDFS), and the secondary end points were iDFS in the Ki-67 Index ≥ 20% patient population, distant relapse-free survival, overall survival (OS), and pharmacokinetics.2

The primary end point of the study was achieved in a subgroup of 2,003 patients with ≥4 positive axillary lymph nodes (ALN), or 1 to 3 positive ALN who either had grade 3 disease and/or a tumor size of ≥ 5 cm, and whose tumors had a Ki-67 score of ≥20%. Compared with endocrine therapy alone, the combination of abemaciclib and endocrine therapy improved iDFS for this subgroup (HR, 0.643; 95% CI, 0.475-0.872; P = .0042).

Additional follow-up conducted post-hoc is what led to the FDA decision. A clinically meaningful benefit was observed with the abemaciclib combination after it had achieved a 37% decrease in the risk of breast cancer recurrence or death compared with standard adjuvant endocrine therapy alone in patients with high risk clinical and pathological features who had a Ki-67 score ≥20% (HR, 0.626; 95% CI, 0.49-0.80). The combination also achieved an absolute benefit in iDFS at an event rate of 7.1% at the 3-year mark. At the time of the post hoc analysis, 104 iDFS events had occurred in the abemaciclib arm compared with 158 in the endocrine therapy-only arm. OS data were not yet mature at the time of the post hoc analysis.3

In terms of safety, 5,591 patients were evaluated. The most common adverse events (AEs) observed with abemaciclib plus endocrine therapy were diarrhea, infections, fatigue, nausea, headache, vomiting, stomatitis, decreased appetite, dizziness, rash, and alopecia. The AE occurred in more than 10% of the treatment arm and occurred 2% more frequently compared with the endocrine therapy-alone arm. The most common laboratory abnormalities of any grade were creatinine increased, white blood cell count decreased, neutrophil count decreased, anemia, lymphocyte count decreased, platelet count decreased, alanine transaminase increased, aspartate transaminase 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+, HER2- early breast cancer represent another important step forward for people who are in need of new treatment options," said Jacob Van Naarden, senior vice president and chief executive officer of Loxo Oncology at Lilly and president, Lilly Oncology, in the press release.1 "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."

Further data supporting the FDA approval of abemaciclib plus endocrine therapy for the adjuvant treatment of adult patients with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20% will be presented on October 14, 2021, during a European Society for Medical Oncology (ESMO) Virtual Plenary.


1. 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. October 13, 2021. Accessed October 13, 2021. https://bit.ly/30dKHMU

2. Harbeck et al. High Ki-67 as a biomarker for identifying patients with high risk early breast cancer treated in monarchE PD2-01. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual.

3. Johnston SRD, Harbeck N, Hegg R, et al; monarchE Committee Members and Investigators. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 38(34): 3987-3998, doi:10.1200/JCO.20.02514.