Efficacy and safety of phosphoinositide 3-kinase inhibitors and AKT-inhibitors in combination with fulvestrant in PIK3CA mutated,HR-positive,HER2-negative invasive breast cancer: A systematic review

Abstract

The treatment paradigm for advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer has advanced rapidly over the last decade. The discovery of mutations in the PIK3CA gene and subsequent development of targeted therapies against this gene, which is mutated in approximately 40% of all HR-positive, HER2-negative breast cancers, has revolutionized treatment. There are currently two Food and Drug Administration (FDA) approved medications for PIK3CA mutated breast cancer—alpelisib and capivasertib. Both medications are considered category 1, or preferred option, by the National Comprehensive Cancer Network (NCCN) in the second-line setting for HR-positive, HER2-negative, PIK3CA mutated advanced or metastatic breast cancer. The purpose of this systematic review is to compare both the efficacy and safety profiles of alpelisib and capivasertib to better inform physicians and patients. A systematic review was conducted and included studies were analyzed for efficacy and safety endpoints. Both medications provide overall survival as well as progression free survival benefits in HR-positive, HER2-negative, PIK3CA mutated breast cancer. Safety profiles between alpelisib and capivasertib were similar. Both medications caused gastrointestinal side effects including nausea, vomiting, and loss of appetite. Capivasertib had a higher incidence of hypertension and rash whereas alpelisib had a higher incidence of hyperglycemia and alopecia. Knowledge of the side effect profiles of these medications is useful to providers as individual patient-specific factors such as comorbidities, preferences, and potential for adverse events to develop are likely to guide treatment decisions as alpelisib and capivasertib have not been compared head-to-head.