Two years of adjuvant abemaciclib+ET resulted in sustained improvement in IDFS (HR=0.68, 5-Year rates:84% abemaciclib+ET vs 76% ET, 8% absolute benefit) in patients with HR+, HER2, node-positive, high-risk EBC. Younger patients (≤40years) often have more aggressive disease. We assessed efficacy/safety data in patients ≤40years and >40years in monarchE.
Patients were randomised 1:1 to ET for ≥5years +/- abemaciclib for 2years. ET switch (tamoxifen, aromatase inhibitors [AI]) was allowed. IDFS/DRFS in 2 subgroups (≤40/>40years) were assessed using Kaplan-Meier method and unstratified Cox model. Safety was summarized by group.
830 patients were ≤40years vs 4807 >40years. 93% of patients ≤40 were premenopausal, 50% received AI as first ET, and 22% had ≥4 comorbidities vs 35%, 71% and 38% among patients >40, respectively. Patients ≤40 generally had higher risk disease vs patients >40 (neoadjuvant chemotherapy receipt:49%vs35%; grade 3:44%vs37%). 84% patients ≤40 on abemaciclib+ET completed the 2-year treatment period. A consistent treatment benefit of abemaciclib+ET vs ET alone in IDFS/DRFS was observed across age groups: IDFS ≤40years (HR=0.61[95%CI:0.44,0.84], 5-Year rates: 84vs73%[Δ10]); IDFS >40years (HR=0.70[95%CI:0.61,0.80], 5-Year rates: 84vs77%[Δ7]) and DRFS ≤40years (HR=0.61[95%CI:0.43,0.86], 5-Year rates: 86vs77%[Δ9]; DRFS >40years (HR=0.70[95%CI:0.60,0.81], 5-Year rates:86vs80%[Δ6]). Of abemaciclib treated patients, 7% patients ≤40 and 4% patients >40 switched from tamoxifen to AI within first 2 years. Grade ≥3 events were similar in abemaciclib+ET arm in ≤40 and >40, 13%vs16% had SAEs and 5%vs8% had Grade 3 diarrhea. Abemaciclib dose reductions/discontinuations due to AEs were less in patients ≤40vs>40 (36%vs45%/8%vs20%).
In patients with high-risk EBC, adjuvant abemaciclib+ET showed consistent and clinically meaningful treatment benefit across age groups with a manageable safety profile. Patients ≤40years 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.