Background
Two years of adjuvant abemaciclib plus endocrine therapy (ET) resulted in sustained improvement in invasive disease-free survival (iDFS) (HR, 0.68, 5-year rates: 84% abemaciclib plus ET vs 76% ET, 8% absolute benefit) in patients with hormone receptor–positive/HER2-negative, node-positive, high-risk early breast cancer. Younger patients (≤ 40 years) often have more aggressive disease. We assessed efficacy/safety data in patients ≤ 40 years and > 40 years in monarchE.
Methods
Patients were randomly assigned 1:1 to ET for 5 years or more with or without abemaciclib for 2 years. ET switch (tamoxifen, aromatase inhibitors [AI]) was allowed. iDFS/distant relapse-free survival (DRFS) in 2 subgroups (≤ 40/> 40 years) were assessed using Kaplan-Meier method and unstratified Cox model. Safety was summarized by group.
Results
A total of830 patients were 40 years or younger vs 4807 who were older than 40 years. Among patients 40 years or younger vs older than 40, 93% vs 35% were premenopausal, 50% vs 71% received AI as first ET, and 22% vs 38% had 4 or more comorbidities. Patients 40 years or younger vs older than 40 generally had higher risk disease (neoadjuvant chemotherapy receipt: 49% vs 35%; grade 3: 44% vs 37%). Among patients 40 years or younger on abemaciclib plus ET, 84% completed the 2-year treatment period. A consistent treatment benefit of abemaciclib plus ET vs ET alone in iDFS/DRFS was observed across age groups: iDFS 40 years or younger (HR, 0.61; 95% CI, 0.44-0.84), 5 year: 84% vs 73% [Δ10]); iDFS older than 40 years (HR, 0.70; 95% CI, 0.61-0.80], 5 year: 84% vs 77% [Δ7]) and DRFS 40 years or younger (HR, 0.61; 95% CI, 0.43-0.86], 5 year: 86% vs 77% [Δ9]); DRFS older than 40 years (HR, 0.70; 95% CI, 0.60-0.81], 5 year: 86% vs 80% [Δ6]). Of abemaciclib-treated patients 40 years or younger vs older than 40, 7% vs 4% switched from tamoxifen to AI within the first 2 years. Grade 3 or higher events were similar in the abemaciclib plus ET arm in those 40 years or younger vs older than 40: 13% vs 16% had serious adverse effects (AEs) and 5% vs 8% had grade 3 diarrhea. Abemaciclib dose reductions/discontinuations due to AEs were lower in patients those 40 years or younger vs older than 40 (36% vs 45%/8% vs 20%).
Conclusion
In patients with high-risk early breast cancer, adjuvant abemaciclib plus ET showed consistent and clinically meaningful treatment benefit across age groups with a manageable safety profile. Patients 40 years or younger had a numerically higher treatment effect and lower rates of abemaciclib discontinuation due to AEs. The versatility of abemaciclib to combine with tamoxifen or AI allows clinicians to switch and optimize ET options to improve tolerability and persistence.
Previously presented at ESMO Breast Cancer 2025.
Study is sponsored by Eli Lilly and Company.
