TY - JOUR
TI - Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study
AU - Rugo, H.S.
AU - O'Shaughnessy, J.
AU - Boyle, F.
AU - Toi, M.
AU - Broom, R.
AU - Blancas, I.
AU - Gumus, M.
AU - Yamashita, T.
AU - Im, Y.-H.
AU - Rastogi, P.
AU - Zagouri, F.
AU - Song, C.
AU - Campone, M.
AU - San Antonio, B.
AU - Shahir, A.
AU - Hulstijn, M.
AU - Brown, J.
AU - Zimmermann, A.
AU - Wei, R.
AU - Johnston, S.R.D.
AU - Reinisch, M.
AU - Tolaney, S.M.
AU - monarchE Committee Members
JO - Annals of oncology: official journal of the European Society for Medical Oncology
PY - 2022
VL - 33
TODO - 6
SP - 616-627
PB - NLM (Medline)
SN - null
TODO - 10.1016/j.annonc.2022.03.006
TODO - abemaciclib;  aminopyridine derivative;  antineoplastic agent;  benzimidazole derivative;  epidermal growth factor receptor 2, breast tumor;  diarrhea;  female;  human;  metabolism;  patient-reported outcome;  quality of life;  tumor recurrence, Aminopyridines;  Antineoplastic Combined Chemotherapy Protocols;  Benzimidazoles;  Breast Neoplasms;  Diarrhea;  Female;  Humans;  Neoplasm Recurrence, Local;  Patient Reported Outcome Measures;  Quality of Life;  Receptor, ErbB-2
TODO - 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. Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
ER -