FDA Widens Indication for Abemaciclib in HR+/HER2–, Node+, High-Risk Breast Cancer


With a broadened FDA label for abemaciclib, patients high-risk breast cancer can now be categorized based only on nodal status, tumor size, and tumor grade.

The FDA has expanded the indication for abemaciclib (Verzenio), in combination with endocrine therapy (ET), for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence.1

With the label expansion, patients with high-risk disease can be categorized solely based on nodal status, tumor size, and tumor grade (4 or more positive nodes, or 1-3 positive nodes and at least one of the following: tumors that are ≥5 cm or grade 3), according to Eli Lily and Company.

The label for abemaciclib was expanded based on findings from the phase 3 monarchE study (NCT03155997) of adjuvant abemaciclib in combination with ET vs adjuvant ET alone in patients with breast cancer. According to results published in The Lancet Oncology, the addition of abemaciclib demonstrated a significant improvement in invasive disease-free survival (iDFS) compared with ET alone. Moreover, the DFS benefit was sustained after the completion of treatment with an absolute increase at 4 years.2 The study also showed a trend toward overall survival (OS) improvement with abemaciclib/ET.1

Sara Tolaney on monarchE and abemaciclib label expansion

Sara M. Tolaney, MD, PhD

“The benefit of adjuvant abemaciclib in patients with hormone-receptor positive breast cancer was seen irrespective of Ki-67, so the decision by the FDA to expand the label and remove Ki-67 from patient selection is wonderful news and great for patients, Sara M. Tolaney, MD, PhD, chief, Division of Breast Oncology, Susan F. Smith Center for Women's Cancer; associate Director, Susan F. Smith Center for Women's Cancer, ;senior physician; and associate professor of Medicine, Harvard Medical School told Targeted OncologyTM

monarchE is a randomized, open-label, phase 3 study that included 5,637 adults with high-risk HR-positive, HER2-negative, node-positive early breast cancer across 2 cohorts.1,2 Aside from the primary end point of iDFS, the secondary end points of the study included iDFS in patients with a Ki-67 index ≥ 20%, distant relapse-free survival, overall survival (OS), and pharmacokinetics.2

Patients received abemaciclib 150 mg with at least 6 hours between doses for up to 2 years. In some cases treatment was stopped when patients showed evidence of disease recurrence or other discontinuation criteria were met. In both treatment arms, ET was administered according to package label, until discontinuation criteria were met.

Eriak Hamilton give statement on the monarchE trial and future of abemaciclib in breast cancer

Erika P. Hamilton, MD

"Our goal in intensifying treatment for early breast cancer is to maintain remission and prevent the recurrence of cancer. The magnitude of benefit seen in the four-year data from the monarchE study reinforces my confidence in adjuvant Verzenio as the standard-of-care for high-risk patients in this setting," said Erika P. Hamilton, MD, medical oncologist, director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute, in a press release.1 "The initial Verzenio FDA approval in early breast cancer was practice-changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them."

At a median follow-up of 42 months (IQR 37-47) in monarchE, the iDFS was superior in the abemaciclib/ET arm vs the ET-alone arm (HR, 0.664; 95% CI 0.578–0.762, nominal P <0.0001). The 4-year DFS rate in the abemaciclib/ET group was 85.8% (95% CI, 84.2-87.3) compared with 79.4% (95% CI, 77.5%–81.1%), showing an absolute difference of 6.4%. Deaths were seen in 5.6% of abemaciclib/ET arm vs 6.1% of the ET-only arm (HR, 0.929; 95% CI 0.748-1.153; P =0.50).

Safety results showed that the most common grade 3/4 adverse events (AEs) in the abemaciclib/ET arm vs the ET arm was neutropenia (19.6% v 0.9%), leukopenia (11.4% v 0.4%), and diarrhea (7.8% v 0.2%). Serious AEs occurred in 15.5% vs 9.1%, respectively.

The monarchE istudy s continuing follow-up of patients to determine the effect of abemaciclib on overall survival.

"This expanded approval will allow us to bring Verzenio to many more women and men with HR-positive, HER2-negative, high-risk early breast cancer in the curative setting – before patients experience recurrence, potentially to incurable metastatic disease," said Jacob Van Naarden, chief executive officer of Loxo@Lilly, in the press release. "The initial adjuvant approval for Verzenio changed the treatment paradigm, and the strength of the monarchE results supporting this approval underscores the role this differentiated CDK4/6 inhibitor can play in reducing the risk of recurrence in early breast cancer."


1. U.S. FDA broadens indication for Verzenio® (abemaciclib) in HR+, HER2-, node-positive, high risk early breast cancer. News release. Eli Lily and Company. March 3, 2023. Accessed March 3, 2023. https://bit.ly/3L3ujns

2. Johnston SR, Toi M, O'Shaughnessy J, et al, Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. Published December 6, 2022. doi: 10.1016/S1470-2045(22)00694-5

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