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


Indication for abemaciclib (Verzenio; Eli Lilly and Company) in combination with endocrine therapy expanded for the adjuvant treatment of adults with hormone receptor–positive, human epidermal growth factor receptor 2-negative, node-positive, early breast cancer with a high risk of recurrence.

The FDA has granted approval to an expanded indication for abemaciclib (Verzenio; Eli Lilly and Company) in combination with endocrine therapy (ET) for the adjuvant treatment of adults with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer with a high risk of recurrence.

The FDA also broadened the indication of the drug in combination with an aromatase inhibitor as initial endocrine-based therapy for patients with HR–positive, HER2-negative advanced or metastatic breast cancer. The expanded indication now includes all adult patients, including pre- and perimenopausal women when paired with ovarian suppression.

Patients deemed to be high risk who are eligible to receive abemaciclib can be identified based on nodal status, tumor size, and tumor grade with the expanded indication, which removes a Ki-67 score requirement for patient selection. Ki-67 is a protein that increases in cells just before division into new cells. An FDA-approved test measures the percentage of tumor cells positive for Ki-67.

"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 4-year data from the monarchE study reinforces my confidence in adjuvant Verzenio as the standard-of-care for high risk patients in this setting," Erika P. Hamilton, MD, medical oncologist, director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute, said in a press release. "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."

Abemaciclib is an oral kinase inhibitor used to treat all stages of HER2-negative breast cancer. The FDA initially approved abemaciclib in 2017 for certain types of HR-positive HER2-negative advanced or metastatic breast cancer. The FDA approved abemaciclib in October 2021 in combination with ET for the adjuvant treatment of patients with HR-positive HER2-negative, node-positive, early breast cancer at a high risk of recurrence and a Ki-67 score greater than or equal to 20%.

The new expanded indicated was based on 4-year findings from the phase 3 monarchE trial (NCT03155997). The trial found that adjuvant abemaciclib plus ET (n = 2555) produced an invasive disease-free survival (iDFS) benefit beyond the 2-year treatment course compared with ET alone (n = 2565). Over time, the absolute difference was found to increase between the treatment arms.

Data show that at 4 years, 85.5% of patients administered abemaciclib plus ET were still free of recurrence compared with 78.6% of patients administered ET alone, which translates to an absolute difference in iDFS of 6.9%.

At 2 years, the absolute difference rate between the treatment arms was 3.1%, which grew to 5.0% at 3 years. Abemaciclib plus ET produced a 35% decrease in the risk of recurrence compared with ET alone (HR, 0.653; 95% CI, 0.567-0.753).

There were no new safety signals noted, and the overall safety data were consistent with was previously reported with abemaciclib. The most frequent adverse effects (AEs) were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache. The most common grade 3 or 4 AEs were neutropenia, leukopenia, diarrhea, and lymphopenia.

The open-label, randomized, phase 3 trial enrolled adults with HR-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence who were at least 18 years of age and had an ECOG performance status of 0 or 1.2 Patients were randomized to receive 2 years of oral abemaciclib at 150 mg twice daily plus physician's choice of standard ET plus tamoxifen or an aromatase inhibitor or ET alone.

The investigators enrolled 5637 patients total, with 91% (n = 5120) enrolled to cohort 1. Patients had a median age of 51 years (range, 22-89), 99% were women, 70% were White, and 53% were premenopausal. Further, 37% previously received neoadjuvant treatment, 59% received adjuvant treatment, and 96% previously received radiotherapy.

A significant improvement in iDFS was observed with abemaciclib plus ET compared with ET alone in the intention-to-treat population, mostly because of the patients in cohort 1, according to the study. Although the data in cohort 2 were immature, more deaths were observed in the investigative cohort compared with the control cohort (n = 10/253 vs n = 5/264). The median duration of exposure to abemaciclib was 24 months.

"This expanded approval will allow us to bring Verzenio to many more women and men with hormone receptor–positive, HER2-negative, high-risk early breast cancer in the curative setting – before patients experience recurrence, potentially to incurable metastatic disease," Jacob Van Naarden, chief executive officer of Loxo@Lilly, said in the 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."


US FDA broadens indication for Verzenio (abemaciclib) in HR+, HER2-, node-positive, high risk early breast cancer. News release. Eli Lilly and Company. March 3, 2023. Accessed March 3, 2023. https://investor.lilly.com/news-releases/news-release-details/

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