Two years of adjuvant abemaciclib combined with endocrine therapy (ET) have previously demonstrated statistically significant and clinically meaningful improvements in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) compared with ET alone in patients with hormone receptor (HR)-positive/HER2-negative, node-positive, high-risk early breast cancer. Updated long-term analysis of this study demonstrates significant improvement in overall survival (OS) of 15.8% in patients receiving abemaciclib plus ET compared with ET alone.

The monarchE trial (NCT03155997) was an open-label, randomized, phase 3 study enrolling patients with HR-positive/HER2-negative, high-risk early breast cancer. Participants were randomized in a 1:1 ratio to receive ET for at least 5 years either alone or in combination with abemaciclib for the first 2 years. High-risk early breast cancer was defined as ≥4 positive axillary lymph nodes (ALNs) or 1 to 3 ALNs with either grade 3 disease and/or tumor size ≥5 cm (cohort 1). Patients with 1 to 3 positive ALNs and a central Ki-67 index ≥20% were enrolled in cohort 2. The intent-to-treat (ITT) population included patients from both cohorts (cohort 1, n=5120; cohort 2, n=517). The Kaplan−Meier method was used, and hazard ratios were calculated using the Cox proportional hazards model. The primary OS analysis (key secondary endpoint) was conducted upon the occurrence of approximately 650 deaths in the ITT population to ensure a minimum follow-up time of ≥5 years.

In the ITT population, with a median follow-up of 6.3 years, 301 deaths occurred in the abemaciclib plus ET arm and 360 deaths in the ET-alone arm. At a median follow-up of 6.3 years, the addition of abemaciclib to ET reduced the risk of death by 15.8% compared with ET alone (hazard ratio, 0.84; 95% confidence interval [CI], 0.72-0.98; 2-sided P=.027), meeting the prespecified boundary for statistical significance. The OS benefit was consistent across all prespecified subgroups. Furthermore, the IDFS and DRFS benefits observed during earlier analyses persisted up to 7 years of follow-up, with hazard ratios of 0.73 (95% CI, 0.66-0.82; P<.0001) for IDFS and 0.75 (95% CI, 0.66-0.84) for DRFS. There was consistent IDFS benefit across prespecified subgroups. Abemaciclib plus ET reduced the risk of IDFS events by 26.6% compared with ET alone. At 7 years, the rates of IDFS and DRFS were 77.4% and 80.0%, respectively, in the abemaciclib plus ET arm, compared with 70.9% and 74.9%, respectively, in the ET-alone arm, yielding absolute benefits of 6.5% for IDFS and 5.1% for DRFS. Most IDFS events involved distant metastatic disease, and abemaciclib plus ET was associated with a reduction in metastases at common sites, while both treatment arms demonstrated low rates of second primary neoplasms. There were approximately 30% fewer patients in the abemaciclib arm living with metastatic disease. Notably, 47.3% of patients in the ET-alone arm received subsequent cyclin-dependent kinase (CDK)4/6 inhibitors in the metastatic setting, compared with 30% in the abemaciclib plus ET arm. Subgroup analyses within cohort 1 revealed consistent benefits in IDFS, DRFS, and OS, aligning with the outcomes observed in the ITT population. Long-term safety data confirmed the tolerability of abemaciclib, with no evidence of delayed toxicities.

The addition of 2 years of adjuvant abemaciclib to ET significantly improved OS in patients with HR-positive/HER2-negative, node-positive, high-risk early breast cancer. Sustained benefits in IDFS and DRFS were observed up to 7 years, reinforcing the long-term efficacy of this combination therapy. These findings, along with the manageable safety profile, establish abemaciclib plus ET as a critical treatment strategy for reducing recurrence and improving survival in patients with high-risk, HR-positive/HER2-negative early breast cancer.

Source: Johnston SR, Martin M, O’Shaughnessy J, et al. monarchE: primary overall survival (OS) results of adjuvant abemaciclib + endocrine therapy (ET) for HR+, HER2-, high-risk early breast cancer (EBC). Presented at: ESMO Congress 2025. October 17, 2025; Berlin, Germany. Abstract LBA13.