Rugo, H SO'Shaughnessy, JBoyle, FToi, MBroom, RBlancas, IGumus, MYamashita, TIm, Y-HRastogi, PZagouri, FSong, CCampone, MSan Antonio, BShahir, AHulstijn, MBrown, JZimmermann, AWei, RJohnston, S R DReinisch, MTolaney, S MmonarchE Committee Members2023-05-032023-05-032022-03-23http://hdl.handle.net/10668/21896In 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. 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. 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'. 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/HER2 negativeHR positiveabemaciclibearly breast cancermonarchEsafetyAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesBreast NeoplasmsDiarrheaFemaleHumansNeoplasm Recurrence, LocalPatient Reported Outcome MeasuresQuality of LifeReceptor, ErbB-2research article35337972open access10.1016/j.annonc.2022.03.0061569-8041http://www.annalsofoncology.org/article/S0923753422003830/pdf