MON-678 Worsening Diabetes Control in Breast Cancer Patients Treated with Alpelisib

Introduction: A new phosphatidylinositol-3-kinase (PI3K) inhibitor, alpelisib (Piqray) has been recently approved for the treatment of breast cancer. Severe hyperglycemia has been reported as an adverse effect. Many breast cancer patients also have diabetes mellitus type 2 which puts them at a higher risk for this adverse effect.1 2 Case description: Patient is a 73 year old Caucasian woman with history of insulin treated type 2 diabetes mellitus and breast cancer who presented to the hospital with a left hip fracture. She has been recently started on alpelisib with worsening glycemic control. Glycemic control improved after alpelisib was held for 5 days. She resumed taking alpelisib and had an up titration of the insulin regimen. During her hospital stay, she suffered from hyperglycemia as high as 558 mg/dl. HbA1c increased to 11.3% from 6.5% reportedly before starting alpelisib. Patient was discharged on an intensified regimen with close follow up. Discussion: Alpelisib is a PI3K inhibitor used in the treatment of postmenopausal women and men with hormone receptor positive, human epidermal growth factor receptor-2 negative, PIK3CA-mutated metastatic breast cancer. It inhibits PI3K which in turn inhibits protein kinase B (AKT). Insulin binds to insulin receptor substrates which activates PI3K, which in turn activates AKT resulting in translocation of the glucose transporter GLUT4 to the plasma membrane causing an uptake of glucose.3 A disruption in this pathway will result in hyperglycemia. Hyperglycemia was reported in 65% of patients with some cases found to be in ketoacidosis. This adverse effect means frequent monitoring of blood glucose is required following initiation of this treatment.4 Conclusion: Alpelisib is a new drug used in the select treatment of breast cancer. It can cause severe hyperglycemia and potential worsening of diabetes. Blood glucose should be monitored closely in patients with diabetes who are treated with alpelisib. References: Giovannucci E et al. Diabetes and Cancer. A consensus report. Diabetes Care 33:1674–1685, 2010. Boyle P et al. Diabetes and breast cancer risk: a meta-analysis. British Journal of Cancer 107, 1608–1617, 2012. Huang, X et al. The PI3K/AKT pathway in obesity and type 2 diabetes. International Journal of Biological Sciences14,1483–1496,2018. Piqray [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp;2019