Abemaciclib Plus Endocrine Therapy Improves Overall Survival in High-Risk Early Breast Cancer

In the global, randomized, open-label, 2-cohort multicenter phase 3 monarchE clinical trial (NCT02246621), abemaciclib (Verzenio; Eli Lilly and Company), plus endocrine therapy (ET) demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to ET alone among individuals with hormone receptor-positive (HR+), HER2-negative, node-positive, high-risk early breast cancer.^1,2

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"Preventing disease relapse and helping patients live longer is the ultimate goal and a high bar in the adjuvant setting. Achieving a statistically significant OS benefit with just two years of [abemaciclib] therapy reinforces its differentiated profile in high-risk HR-positive, HER2-negative early breast cancer," Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in a news release.¹

monarchE Overview and Results

A total of 5637 adults with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence were included in the study. Cohort 1 included 5120 patients with either 4 or more positive lymph nodes or 1 to 3 positive nodes along with a tumor that was at least 5 cm or grade 3. The second cohort included 517 patients, including 1 to 3 positive nodes and a Ki-67 score of at least 20%. Patients in cohort 1 were the FDA-approved population, and individuals in cohort 2 did not meet the criteria.¹

In both cohorts, individuals were randomly assigned to receive either 150 mg of abemaciclib twice daily with standard-of-care adjuvant ET or standard-of-care adjuvant ET alone for a 2-year period.¹

The primary end point of the study was invasive disease-free survival, defined as the time to breast cancer recurrence, a new cancer, or death. The key secondary end point was OS.¹

The results demonstrated that abemaciclib with ET demonstrated improvements in OS compared to ET alone, reinforcing that 2 years of abemaciclib with ET is the standard of care in adults with HR-positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence.¹

"These data validate [abemaciclib] as the standard-of-care for patients with node-positive, high-risk disease and increase the urgency to ensure all eligible patients are treated,” Naarden said in the news release.¹

Understanding HR+ and HER2- Breast Cancer

Breast cancer is marked as the second most diagnosed cancer and the fourth-leading cause of cancer death worldwide, accounting for nearly 666,000 deaths in 2022 alone. Among all breast cancer cases, approximately 70% are the HR-positive, HER2-negative subtype, which means the tumor has receptors for both hormones—estrogen and progesterone—and the HER2 protein. If detected in an early stage, the prognosis is favorable; however, individuals that are high risk are 3 times more likely than those with low-risk characteristics to experience recurrence. High-risk recurrence in HR-positive, HER2-negative early breast cancer includes positive nodal status, the number of positive nodes, large tumor size, and high tumor grade.¹

Abemaciclib for Breast Cancer Treatment

Abemaciclib was the first CDK4/6 inhibitor approved to treat node-positive, high-risk early breast cancer, receiving an FDA-approved expansion in March 2023 with ET for the adjuvant treatment of adults with HR-positive, HER2-negative breast cancer at high risk of recurrence.^1,3

The drug is administered as a twice-daily oral tablet in 50 mg, 100 mg, 150 mg, and 200 mg. In addition to its early-stage breast cancer indications, abemaciclib is also used for advanced or metastatic breast cancer, either as an initial treatment in combination with an aromatase inhibitor or in combination with fulvestrant (Faslodex; AstraZeneca) for patients whose disease has progressed after previous ET. Additionally, it can be used alone for advanced or metastatic breast cancer in patients whose disease has progressed after both ET and prior chemotherapy.¹

REFERENCES

1. Lilly's Verzenio® (abemaciclib) increases overall survival in HR+, HER2-, high-risk early breast cancer with two years of therapy. Eli Lilly and Company. News release. August 27, 2025. Accessed September 2, 2025. https://www.prnewswire.com/news-releases/lillys-verzenio-abemaciclib-increases-overall-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-therapy-302539340.html

2. A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal Women With Breast Cancer (MONARCH 3) Updated April 20, 2024. Accessed September 2, 2025. https://clinicaltrials.gov/study/NCT02246621

3. FDA expands early breast cancer indication for abemaciclib with endocrine therapy. FDA. News release. March 3, 2023. Accessed September 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-early-breast-cancer-indication-abemaciclib-endocrine-therapy