@article{3219290,
    title = "Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study",
    author = "Rugo, H.S. and O'Shaughnessy, J. and Boyle, F. and Toi, M. and Broom, R. and Blancas, I. and Gumus, M. and Yamashita, T. and Im, Y.-H. and Rastogi, P. and Zagouri, F. and Song, C. and Campone, M. and San Antonio, B. and Shahir, A. and Hulstijn, M. and Brown, J. and Zimmermann, A. and Wei, R. and Johnston, S.R.D. and Reinisch, M. and Tolaney, S.M. and monarchE Committee Members",
    journal = "Annals of oncology: official journal of the European Society for Medical Oncology",
    year = "2022",
    volume = "33",
    number = "6",
    pages = "616-627",
    publisher = "NLM (Medline)",
    doi = "10.1016/j.annonc.2022.03.006",
    keywords = "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",
    abstract = "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."
}