Adjuvant abemaciclib combined with endocrine therapy (ET): updated results from monarchE

Objective Adjuvant abemaciclib (CDK4&6 inhibitor)+ET provides significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in HR+, HER2-, node+, high-risk early breast cancer (EBC). Updated results with 27-month median follow-up are presented.

Materials/Methods Patients were randomized (1:1) to receive ET for up to 10 years +/- abemaciclib for 2 years. Patients had ≥4+ axillary lymph nodes (ALN), or 1-3+ ALN and either grade-3 disease or tumor≥5 cm (Cohort-1), or 1-3+ ALN and centrally tested Ki-67 ≥20% (Cohort-2). For intent-to-treat (ITT) (cohort 1+2) and Ki-67 populations, hazard ratio (HR) was estimated using Cox proportional hazard model (data cutoff=1-April-2021). Exploratory analyses estimated piecewise HR within each year in ITT.

Results With 90% patients having completed/discontinued 2-year study treatment period, IDFS and DRFS benefit was maintained (HR=0.696; 95%CI=0.588,0.823; HR=0.687; 95%CI=0.571,0.826). At 3 years, absolute improvement in IDFS/DRFS rates=5.4/4.2%. Abemaciclib benefit deepened during treatment period (estimated IDFS/DRFS piecewise HR at year 0-1=0.795/0.732, year 1-2=0.681/0.675) and persisted after treatment period (2+ year IDFS/DRFS piecewise HR=0.596/0.692). IDFS rates at 3 years in Cohort-1 control arm (79.0%/87.2% in Ki-67 High/Low) confirmed prognostic value of Ki-67; abemaciclib benefit was consistent regardless of Ki-67 index (HR=0.626/0.704 in Ki-67 High/Low). Adverse event profile was similar to prior analysis.

Summary Benefit of adjuvant abemaciclib+ET is strengthened within and beyond the 2-year treatment period in HR+, HER2-, node+, high-risk EBC. High Ki-67 was prognostic, but not predictive of abemaciclib benefit. Safety profile remains acceptable for patients with EBC treated with curative intent.

Publication History

Article published online:
21 June 2022