Abemaciclib Ups Overall Survival in High-Risk Breast Cancer

By: Liam Davenport

From: medscape.com

TOPLINE:

Patients with hormone receptor positive (HR+), HER2-negative (HER2-), high-risk early breast cancer experience a significant overall survival benefit with the addition of the CDK4/6 inhibitor abemaciclib to endocrine therapy, as well as a reduction in rates of metastatic disease, according to an analysis of data from the monarchE trial presented at the ESMO Congress 2025.

METHODOLOGY:

• Previously reported results from monarchE showed that adjuvant abemaciclib plus endocrine therapy is associated with a significant improvement in invasive disease-free survival (IDFS) over endocrine therapy alone and is now considered a standard of care.
• A previous 5-year interim analysis, after a median follow-up of 54 months, showed the IDFS benefit with abemaciclib was maintained, and indicated the drug was associated with a favorable overall survival trend. The current presentation offered the primary overall survival analysis.
• The trial enrolled patients with HR+, HER2-, node-positive, high-risk early breast cancer, with high risk defined by clinical pathological features or, additionally, Ki-67 status.
• The patients were randomly assigned to abemaciclib 150 mg twice daily plus endocrine therapy or endocrine therapy alone for 2 years. Both groups then continued on endocrine therapy alone for 3-8 years, depending on the clinical indication.
• The primary endpoint was IDFS, with overall survival a key secondary endpoint.

TAKEAWAY:

• After a median follow-up of 6.3 years, abemaciclib plus endocrine therapy was associated with a statistically significant improvement in overall survival, at a hazard ratio for death vs endocrine therapy alone of 0.842 (P = .0273), or an absolute difference of 1.8%. The benefit was seen across prespecified subgroups.
• The combination was also associated with a reduction in the proportion of patients living with metastatic disease, at 6.4% vs 9.4% with endocrine therapy alone.
• The previously reported IDFS benefit with abemaciclib was also sustained, at a hazard ratio vs endocrine therapy alone of 0.734 (P < .0001), again across prespecified subgroups.
• The safety results were consistent with earlier analyses, with 7.5% of abemaciclib patients and 8.1% of endocrine therapy alone patients experiencing a serious adverse event on long-term follow-up.

IN PRACTICE:

Abemaciclib plus endocrine therapy “has shown a statistically significant improvement in overall survival in the intent-to-treat population, reducing the risk of death by 15.8%, and more importantly, clinically significant, meaningful changes in metastatic disease,” said study presenter Stephen R. Johnston, MD, PhD, Head of Breast Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London.

He added that abemaciclib “represents the first CDK4/6 inhibitor to achieve a statistically significant improvement in overall survival for these high-risk, node-positive patients.”

SOURCE:

The research, which Johnston presented October 17 at the ESMO Congress 2025 (Abstract LBA13), was funded by Eli Lilly and Company. The study results were simultaneously published in the Annals of Oncology.