Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study

Ann Oncol. 2022 Jun;33(6):616-627. doi: 10.1016/j.annonc.2022.03.006. Epub 2022 Mar 23.


Background: In monarchE, abemaciclib plus endocrine therapy (ET) as adjuvant treatment of hormone receptor-positive, human epidermal growth factor 2-negative, high-risk, early breast cancer (EBC) demonstrated a clinically meaningful improvement in invasive disease-free survival versus ET alone. Detailed safety analyses conducted at a median follow-up of 27 months and key patient-reported outcomes (PROs) are presented.

Patients and methods: The safety population included all patients who received at least one dose of study treatment (n = 5591). Safety analyses included incidence, management, and outcomes of common and clinically relevant adverse events (AEs). Patient-reported health-related quality of life, ET symptoms, fatigue, and side-effect burden were assessed.

Results: The addition of abemaciclib to ET resulted in higher incidence of grade ≥3 AEs (49.7% versus 16.3% with ET alone), predominantly laboratory cytopenias [e.g. neutropenia (19.6%)] without clinical complications. Abemaciclib-treated patients experienced more serious AEs (15.2% versus 8.8%). Discontinuation of abemaciclib and/or ET due to AEs occurred in 18.5% of patients, mainly due to grade 1/2 AEs (66.8%). AEs were managed with comedications (e.g. antidiarrheals), abemaciclib dose holds (61.7%), and/or dose reductions (43.4%). Diarrhea was generally low grade (grade 1/2: 76%); grade 2/3 events were highest in the first month (20.5%), most were short-lived (≤7 days) and did not recur. Venous thromboembolic events (VTEs) were higher with abemaciclib + ET (2.5%) versus ET (0.6%); in the abemaciclib arm, increased VTE risk was observed with tamoxifen versus aromatase inhibitors (4.3% versus 1.8%). PROs were similar between arms, including being 'bothered by side-effects of treatment', except for diarrhea. At ≥3 months, most patients reporting diarrhea reported 'a little bit' or 'somewhat'.

Conclusions: In patients with high-risk EBC, adjuvant abemaciclib + ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile.

Trial registration: NCT03155997.

Keywords: HER2 negative; HR positive; abemaciclib; early breast cancer; monarchE; safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Benzimidazoles
  • Breast Neoplasms* / metabolism
  • Diarrhea / drug therapy
  • Female
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Patient Reported Outcome Measures
  • Quality of Life
  • Receptor, ErbB-2* / metabolism


  • Aminopyridines
  • Benzimidazoles
  • abemaciclib
  • Receptor, ErbB-2

Associated data