Alpelisib is an α-selective phosphatidylinositol 3-kinase inhibitor used for treating
hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2-),
PIK3CA-mutated locally advanced or metastatic breast cancer following disease progression
on or after endocrine therapy. Hyperglycemia is an on-target effect of alpelisib affecting
approximately 60% of treated patients, and sometimes necessitating dose reductions,
treatment interruptions, or discontinuation of alpelisib. Early detection of hyperglycemia
and timely intervention have a key role in achieving optimal glycemic control and
maintaining alpelisib dose intensity to optimize the benefit of this drug. A glycemic
support program implemented by an endocrinology-oncology collaborative team may be
very useful in this regard. Lifestyle modifications, mainly comprising a reduced-carbohydrate
diet, and a designated stepwise, personalized antihyperglycemic regimen, based on
metformin, sodium-glucose co-transporter 2 inhibitors, and pioglitazone, are the main
tools required to address the insulin-resistant hyperglycemia induced by alpelisib.
In this report, based on the consensus of 14 oncologists and seven endocrinologists,
we provide guidance for hyperglycemia management strategies before, during, and after
alpelisib therapy for HR+, HER2-, PIK3CA-mutated breast cancer, with a focus on a
proactive, multidisciplinary approach.
