A multidisciplinary approach to optimizing care of patients treated with alpelisib

• Published in: Breast (Edinburgh) 2022-02, Vol.61, p.156-167
• Main Authors: Rugo, Hope S., Lacouture, Mario E., Goncalves, Marcus D., Masharani, Umesh, Aapro, Matti S., O'Shaughnessy, Joyce A.
• Format: Article
• Language: English
• Subjects: AE management; Alpelisib; Antineoplastic Combined Chemotherapy Protocols; Breast cancer; Breast Neoplasms - drug therapy; Female; Humans; Phosphatidylinositol 3-Kinases; PIK3CA; Review; Thiazoles - therapeutic use
• ISSN: 0960-9776; 1532-3080
• DOI: 10.1016/j.breast.2021.12.016

The oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) 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. Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs. 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 PI3Kα 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. Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach. •Alpelisib-associated AEs are generally manageable and reversible•PI3K inhibitor-associated hyperglycemia is an on-target and transient event•Use of prophylactic antihistamines may reduce onset and severity of rash•Enhanced monitoring and management guidance results in fewer drug discontinuations•Further studies are ongoing to optimize management of alpelisib-associated AEs