PMID- 32955138 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20231110 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 26 IP - 1 DP - 2021 Jan TI - Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. PG - e53-e65 LID - 10.1002/onco.13531 [doi] AB - BACKGROUND: Abemaciclib demonstrated efficacy in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Here we provide a comprehensive summary of the most common adverse events (AEs), their management, and whether AEs or dose reductions influenced progression-free survival (PFS), in the MONARCH 2 and 3 trials. MATERIALS AND METHODS: Incidence of the most clinically relevant AEs, management, and outcomes were summarized. Time-dependent covariate analyses examined the impact of dose reductions on PFS. PFS was estimated for patients with and without early onset of diarrhea or neutropenia. RESULTS: The most frequently reported AE was diarrhea, with clinically significant diarrhea (grade >/=2) reported for 42.8% of patients taking abemaciclib. Median time to onset was 1 week, and duration ranged from 6 to 12 days, depending on grade and study. Diarrhea was adequately managed by antidiarrheal medication (72.8%), dose omissions (17.3%), and reductions (16.7%). The highest rates of grade >/=2 diarrhea were observed in the first cycles and decreased in subsequent cycles. Neutropenia (grade >/=3) occurred in 25.4% of abemaciclib-treated patients. Neutropenia resolved with dose omissions (16.8%) and/or dose reductions (11.2%). Incidence of febrile neutropenia (0.7%) or other relevant grade >/=3 hematological events (<9%) was low. Venous thromboembolic events (5.3%) were primarily treated with anticoagulants. Interstitial lung disease/pneumonitis (3.4%) was treated with corticosteroids and/or antibiotics. PFS benefit of abemaciclib was not impacted by dose reductions or early onset of toxicities. CONCLUSION: Abemaciclib was generally well tolerated. The most common AEs were effectively managed by supportive medications, and/or dose adjustments, with no detriment to PFS. IMPLICATIONS FOR PRACTICE: Treatment with abemaciclib plus fulvestrant or nonsteroidal aromatase inhibitors is generally well tolerated in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. In MONARCH 2 and MONARCH 3, any-grade diarrhea and grade >/=3 neutropenia were effectively managed with supportive medication and/or dose adjustment. Venous thromboembolic events were treated with anticoagulants and did not often require treatment discontinuation. Interstitial lung disease/pneumonitis was infrequent and treated with corticosteroids and/or antibiotics. Clinicians should be aware of and implement management strategies, including dose adjustments according to local labels, for commonly occurring and serious adverse events to ensure continued treatment and optimize clinical benefit/risk ratio. CI - (c) 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press. FAU - Rugo, Hope S AU - Rugo HS AUID- ORCID: 0000-0001-6710-4814 AD - University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA. FAU - Huober, Jens AU - Huober J AD - Universittatsklinikum Ulm, Ulm, Germany. FAU - Garcia-Saenz, Jose A AU - Garcia-Saenz JA AD - Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain. FAU - Masuda, Norikazu AU - Masuda N AD - National Hospital Organization Osaka National Hospital, Osaka, Japan. FAU - Sohn, Joo Hyuk AU - Sohn JH AD - Yonsei Cancer Center, Seoul, Republic of Korea. FAU - Andre, Valerie A M AU - Andre VAM AD - Eli Lilly and Company, Paris, France. FAU - Barriga, Susana AU - Barriga S AD - Eli Lilly and Company, Madrid, Spain. FAU - Cox, Joanne AU - Cox J AD - Eli Lilly and Company, Surrey, United Kingdom. FAU - Goetz, Matthew AU - Goetz M AD - Mayo Clinic, Rochester, Minnesota, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201009 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Aminopyridines) RN - 0 (Benzimidazoles) RN - 22X328QOC4 (Fulvestrant) RN - 60UAB198HK (abemaciclib) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM EIN - Oncologist. 2021 Mar;26(3):e522. PMID: 33660385 CIN - Oncologist. 2021 Jul;26(7):e1285. PMID: 33818868 CIN - Oncologist. 2021 Jul;26(7):e1286-e1287. PMID: 33826783 MH - Aminopyridines MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Benzimidazoles MH - *Breast Neoplasms/drug therapy MH - Female MH - Fulvestrant/therapeutic use MH - Humans MH - Receptor, ErbB-2/therapeutic use PMC - PMC7794176 OTO - NOTNLM OT - Abemaciclib OT - Advanced breast cancer OT - Diarrhea OT - Neutropenia OT - Safety COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2020/09/22 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/01/01 CRDT- 2020/09/21 08:42 PHST- 2020/04/24 00:00 [received] PHST- 2020/08/14 00:00 [accepted] PHST- 2020/09/22 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/09/21 08:42 [entrez] PHST- 2021/01/01 00:00 [pmc-release] AID - ONCO13531 [pii] AID - 10.1002/onco.13531 [doi] PST - ppublish SO - Oncologist. 2021 Jan;26(1):e53-e65. doi: 10.1002/onco.13531. Epub 2020 Oct 9.