Alpelisib-Induced Hyperglycemia in PIK3CA⁺ Breast Cancer Patients

Alpelisib is a phosphatidylinositol 3-kinase inhibitor approved by the US Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer with PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α) mutation. In recent years a number of adverse effects have been observed to be associated with this therapy, the most notable of which is hyperglycemia. A literature search was conducted to include case studies, case series, systematic reviews, and meta-analyses within the last 10 years that evaluated patients with PIK3CA-mutated hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer. Hyperglycemia was a notable adverse effect that was found in the majority of patients without preexisting diabetes mellitus. Patients with hyperglycemia were in the high-risk groups of advanced age, prediabetes mellitus or history of insulin resistance, increased body mass index, increased blood monocyte count, and increased hemoglobin A1c (glycated hemoglobin). Hyperglycemia was manageable with antihyperglycemic agents and dose modification/discontinuation of alpelisib with no severe progression. Other notable adverse effects were rash, stomatitis, diarrhea, pneumonitis, reduced appetite, elevated liver enzymes, nausea, fatigue, and rare reports of diabetic ketoacidosis. This literature review aims to highlight the incidence and risk factors of alpelisib-induced hyperglycemia in greater depth.