PMID- 35016012 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20230917 IS - 1532-3080 (Electronic) IS - 0960-9776 (Print) IS - 0960-9776 (Linking) VI - 61 DP - 2022 Feb TI - A multidisciplinary approach to optimizing care of patients treated with alpelisib. PG - 156-167 LID - S0960-9776(21)01023-7 [pii] LID - 10.1016/j.breast.2021.12.016 [doi] AB - PURPOSE: The oral, alpha-specific phosphatidylinositol-3-kinase (PI3Kalpha) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib. METHODS: Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs. RESULTS: The most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kalpha inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs-in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment. CONCLUSION: Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Rugo, Hope S AU - Rugo HS AD - Department of Medicine (Hematology/Oncology), University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Electronic address: Hope.Rugo@ucsf.edu. FAU - Lacouture, Mario E AU - Lacouture ME AD - Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: LacoutuM@mskcc.org. FAU - Goncalves, Marcus D AU - Goncalves MD AD - Division of Endocrinology, Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA. Electronic address: mdg9010@med.cornell.edu. FAU - Masharani, Umesh AU - Masharani U AD - Department of Medicine (Endocrinology), University of California San Francisco, San Francisco, CA, USA. Electronic address: umesh.masharani@ucsf.edu. FAU - Aapro, Matti S AU - Aapro MS AD - Department of Oncology, Genolier Cancer Centre, Clinique de Genolier, Genolier, Switzerland. Electronic address: maapro@genolier.net. FAU - O'Shaughnessy, Joyce A AU - O'Shaughnessy JA AD - Baylor University Medical Center Texas Oncology, US Oncology, Dallas, TX, USA. Electronic address: joyce.oshaughnessy@usoncology.com. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Review DEP - 20211227 PL - Netherlands TA - Breast JT - Breast (Edinburgh, Scotland) JID - 9213011 RN - 0 (Thiazoles) RN - 08W5N2C97Q (Alpelisib) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols MH - *Breast Neoplasms/drug therapy MH - Female MH - Humans MH - *Phosphatidylinositol 3-Kinases MH - Thiazoles/therapeutic use PMC - PMC8749445 OTO - NOTNLM OT - AE management OT - Alpelisib OT - Breast cancer OT - PIK3CA COIS- Declaration of competing interest H.S. Rugo: Institution research funding from Pfizer, Novartis, Eli Lilly, Genentech, MacroGenics, Merck, OBI Pharma, Eisai, Immunomedics, Daiichi, Odonate, and Seattle Genetics; travel support from Daiichi, AstraZeneca, Novartis, Pfizer, Mylan, and Merck; consulting/advisory income from Puma and Celltrion. M.E. Lacouture: Consulting from Novartis, Varsona, Innovaderm, Novocure, QED, Seagen, Lutris, DFB, JnJ, Deciphera, Onquality, TWIBiotech, Azitra, Janssen, EMD Serono, and Bicara; research funding from Novartis, AZ, JnJ, Onquality, and Novocure. M.D. Goncalves: Personal fees from Novartis, grants from Pfizer, and personal fees from Petra Pharma, Scorpion Therapeutics, and Faeth Therapeutics, outside the submitted work; patent (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and patent for The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment pending; and owns stock in Faeth Therapeutics. U. Masharani: Research funding from Clementia Pharmaceuticals. M.S. Aapro: Consulting/advisory role in Amgen, BMS, Daiichi Sankyo, Fresenius Kabi, G1 Therapeutics, Genomic Health, Helsinn Healthcare, Merck, Merck KGaA, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro, and Vifor Pharma; speakers' bureau at Accord Research, Amgen, Biocon, Dr Reed, Genomic Health, Helsinn Healthcare, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Taiho Pharmaceutical, Tesaro, and Vifor Pharma; research funding from Helsinn Healthcare, Novartis, Pierre Fabre, and Sandoz. J.A. O'Shaughnessy: Personal fees from AbbVie, Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeutics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, Pfizer, Puma Biotechnology, Prime Oncology, Roche, Seattle Genetics, and Syndax Pharmaceuticals, outside the submitted work. EDAT- 2022/01/12 06:00 MHDA- 2022/02/09 06:00 PMCR- 2021/12/27 CRDT- 2022/01/11 20:09 PHST- 2021/10/20 00:00 [received] PHST- 2021/12/23 00:00 [revised] PHST- 2021/12/26 00:00 [accepted] PHST- 2022/01/12 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2022/01/11 20:09 [entrez] PHST- 2021/12/27 00:00 [pmc-release] AID - S0960-9776(21)01023-7 [pii] AID - 10.1016/j.breast.2021.12.016 [doi] PST - ppublish SO - Breast. 2022 Feb;61:156-167. doi: 10.1016/j.breast.2021.12.016. Epub 2021 Dec 27.