Abemaciclib/Endocrine Therapy Improves OS in HR+/HER2– Early Breast Cancer

Results from the monarchE study showed a statistically significant OS improvement with abemaciclib plus ET for patients with HR+/HER2– early breast cancer.

A statistically significant and clinically meaningful improvement in overall survival (OS) was observed with abemaciclib (Verzenio) plus endocrine therapy (ET) vs ET alone for patients with hormone receptor–positive (HR+), HER2-negative (HER2–), node-positive high-risk early breast cancer, according to a press release from Eli Lilly and Company.1

Results from the 7-year analysis of the phase 3 monarchE trial (NCT03155997) found additional sustained benefit with invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS). The safety profile remained unchanged from previous reports. Additional results will be presented at an upcoming medical meeting.

"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 HR+, HER2– early breast cancer," Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in the press release.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."

In January 2024, 5-year efficacy outcomes from monarchE were published in the Journal of Clinical Oncology.2 At the data cutoff of July 3, 2023, the median follow-up time was 54 months. A total of 5637 patients were enrolled into either cohort 1 (n = 5120), with patients who had at least 4 positive pathologic axillary lymph nodes (pALNs) or 1 to 3 pALNs with additional high-risk features of either grade 3 disease or a tumor of 5 cm or more; while cohort 2 (n = 517) had patients with 1 to 3 pALNs and central Ki-67 of 20% or more.

The intent-to-treat population included patients from cohorts 1 and 2 who were randomly assigned 1:1 to receive at least 5 years of ET with or without abemaciclib for 2 years.

A total of 80% of patients were followed for at least 4 years. Abemaciclib showed a sustained benefit in reducing the risk of developing an IDFS event (HR, 0.680; 95% CI, 0.599-0.772; P <.001). At 24 months, the IDFS rates were 92.7% vs 89.9%, at 36 months they were 89.2% vs 84.4%, at 48 months they were 86.0% vs 80.0%, and at 60 months they were 83.6% vs 76.0% between the abemaciclib and ET alone arms, respectively.

An improvement in DRFS was noted with the abemaciclib arm (HR, 0.675; 95% CI, 0.588-0.774; P <.001). The DRFS rates at 24 months were 94.0% vs 91.5%, at 36 months were 90.9% vs 86.7%, at 48 months were 88.4% vs 83.1%, and at 60 months were 86.0% vs 79.2% between the abemaciclib and ET arms, respectively.

Regarding OS, the HR was 0.903 (95% CI, 0.749-1.088; P = .284).

In the abemaciclib plus ET arm, 208 deaths had occurred at the time of the interim analysis compared with 234 in the ET alone arm. During study follow-up, 84.0% of patients were alive in the abemaciclib arm vs 81.4% in the ET alone arm, while 8.6% and 10.3% withdrew or were lost to follow-up.

In cohort 1, the IDFS, DRFS, and OS were consistent with the ITT population, and IDFS and DRFS were consistent across all subgroups. For patients with Ki-67 of 20% or more, higher IDFS and DRFS event rates were observed.

References

1. Lilly's Verzenio® (abemaciclib) increases overall survival in HR+, HER2-, high-risk early breast cancer with two years of therapy. News release. Eli Lilly Company. August 27, 2025. Accessed August 28, 2025. https://tinyurl.com/mryrjbe5
2. 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. 2024;42(9):987-993. doi:10.1200/JCO.23.01994