Adjuvant Abemaciclib Plus Endocrine Therapy Improves OS in High-Risk HR+/HER2– Breast Cancer

Adjuvant abemaciclib (Verzenio) plus 2 years of endocrine therapy led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs endocrine therapy alone in patients with high-risk, node-positive, hormone receptor–positive, HER2-negative early breast cancer, according to topline findings from the primary OS analysis of the phase 3 monarchE trial (NCT03155997).¹

Sustained benefit in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) was also upheld in the abemaciclib arm, according to findings from the 7-year landmark analysis.

At the time of the analysis, all patients had completed or discontinued the two-year course of abemaciclib, and no new safety signals were reported with the agent.

Further results will be shared at an upcoming medical conference, submitted for publication in a peer-reviewed journal, and discussed with regulatory agencies.

“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 2 years of [abemaciclib] therapy reinforces its differentiated profile in high-risk hormone receptor–positive, HER2-negative early breast cancer,” Jacob Van Naarden, executive vice president and president of Lilly Oncology, stated in a news release. “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.”

Background and Prior Data From monarchE

The monarchE studty was a global, randomized, open-label, multicenter phase 3 trial that enrolled 5,637 adults with hormone receptor–positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.

The study comprised 2 cohorts. In cohort 1 (n = 5120), patients had to have 4 or more positive nodes or 1 to 3 positive nodes and at least one of the following: tumors that were 5 cm or greater or grade 3. In cohort 2 (n = 517), patients had to have 1 to 3 positive nodes and a Ki-67 score of at least 20%. Patients in each cohort were randomly assigned 1:1 to receive 150 mg of abemaciclib twice daily plus endocrine therapy in the adjuvant setting (cohort 1, n = 2555; cohort 2, n = 253) or adjuvant endocrine therapy alone (cohort 1, n = 2565; cohort 2, n = 264). Treatment was given for 2 years. Endocrine therapy could be continued for at least 5 years if deemed medically necessary.

The primary end point was IDFS. OS was a key secondary end point, in addition to DRFS and IDFS for patients with a Ki-67 score of 20% or greater.² The statistical design for measuring OS was adjusted after the primary IDFS analysis to increase the number of required OS events from 390 to 650 to allow for a minimum follow-up of 5 years.¹

Data from the first analysis of the trial presented at the 2020 ESMO Congress demonstrated that the study met its primary end point, reducing the likelihood of an IDFS event by 25.3% with the addition of abemaciclib to adjuvant endocrine therapy (HR, 0.747; 95% CI, 0.598-0.932; 2-sided P = .0096).³

Five-year efficacy findings published in the Journal of Clinical Oncology in 2024 with a median follow-up of 54 months revealed that IDFS (HR, 0.680; 95% CI, 0.599-0.772) and DRFS (HR, 0.675; 95% CI, 0.588-0.774) continued to favor abemaciclib vs endocrine therapy alone.⁴

Moreover, the absolute improvement in 5-year IDFS and DRFS rates in the investigational and control arms were 7.6% and 6.7%, respectively, increasing from respective 4-year rates of 6% and 5.3% and respective 3-year rates of 4.8% and 4.1%.

Abemaciclib’s Adjuvant Approval History

On October 12, 2021, the FDA approved abemaciclib for use as adjuvant therapy in combination with endocrine therapy for the treatment of patients with hormone receptor–positive, HER2-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of 20% or greater, as determined by an FDA approved test.⁵

The initial approval was based on findings from monarchE, which showed a statistically significant improvement in IDFS with abemaciclib in the population of patients with a Ki-67 score of at least 20% (n = 2003; HR, 0.626; 95% CI, 0.488-0.803; P = .0042). The 36-month IDFS rate was 86.1% (95% CI, 82.8%-88.8%) with abemaciclib vs 79.0% (95% CI, 75.3%-82.3%) with endocrine therapy alone.

The agency later amended the approval on March 3, 2023, to remove the requirement threshold for Ki-67 expression, instead defining high risk as having either at least 4 pathologic axillary lymph nodes or 1 to 3 pathologic axillary lymph nodes and either tumor grade 3 or a tumor size of 50 mm or greater.⁶

Within the intention-to-treat population, IDFS was significantly improved with abemaciclib vs endocrine therapy alone (HR, 0.653; 95% CI, 0.567-0.753). The 48-month IDFS rates were 85.5% (95% CI, 83.8%-87.0%) with abemaciclib and 78.6% (95% CI, 76.7%-80.4%) with endocrine therapy alone. Because more deaths had been reported in the investigational vs control arm of cohort 2, the existing indication is limited to cohort 1.

References

1. Lilly’s Verzenio (abemaciclib) increases overall survival in HR+, HER2-, high-risk early breast cancer with two years of therapy. Lilly. News release. August 27, 2025. Accessed August 27, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-verzenior-abemaciclib-increases-overall-survival-hr-her2
2. Endocrine therapy with or without abemaciclib (LY2835219) following surgery in participants with breast cancer (monarchE). ClinicalTrials.gov. Updated April 20, 2025. Accessed August 27, 2025. https://www.clinicaltrials.gov/study/NCT03155997
3. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high risk, early breast cancer (monarchE). Ann Oncol. 2020;31(4). Abstract: LBA5_PR.
4. Rastogi P, O’Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor–positive, human epidermal growth factor receptor 2–negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol. 2025;42(9):987-993. doi:10.1200/JCO.23.01994
5. FDA approves abemaciclib with endocrine therapy for early breast cancer. FDA. Updated October 13, 2021. Accessed August 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-abemaciclib-endocrine-therapy-early-breast-cancer
6. FDA expands early breast cancer indication for abemaciclib with endocrine therapy. FDA. March 3, 2023. Accessed August 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-early-breast-cancer-indication-abemaciclib-endocrine-therapy