MON-LB128 Phosphoinositide 3-Kinase (PI3K) Inhibitor Induced Hyperglycemia With Alpelisib

Abstract

Intorduction: Breast cancer is estimated to be the third leading cause of cancer-related death in women. A commonly mutated pathway in breast cancer is the phosphoinositide-3-kinase (PI3K) pathway. Newer agents inhibiting PI3K are now available for the treatment of advanced cancers. Metabolic complications of new onset diabetes/hyperglycemia and hyperlipidemia are commonly seen. The precise mechanism through which PI3K inhibitors cause hyperglycemia is unknown. We present a patient who developed hyperglycemia within 2 weeks of starting alpelisib. Clinical Case: A 68 y.o female with history of metastatic invasive lobular carcinoma of the right breast HR-positive, HER-2 negative who presents for evaluation of hyperglycemia. She was diagnosed with metastatic breast carcinoma and failed multiple treatment options. She was started on alpelisib 2 weeks prior and had no history of glucose intolerance. Her pretreatment HbA1c was 5.5% (n <5.7%). After initiation of alpelisib, fasting blood glucose ranged between 100-140 mg/dL (n 100-125 mg/dL), while post-prandial blood glucose ranged between 150-300 mg/dL (n <140 mg/dl). Her HbA1c rose to 7% (n <5.7%). She did not manifest any macrovascular or microvascular complications, but did have a family history of type 2 diabetes mellitus. After initially being started on metformin, the dose increased to 1500 mg daily with the addition of glimepiride 1 mg. She eventually achieved stable euglycemia on metformin alone.Conclusion: Hyperglycemia has been reported to commonly occur with PI3K inhibitor therapy, the mechanism of which is poorly understood. One purposed mechanism is the effect on AMP kinase pathway which may also affect the efficacy of metformin. Here, we present a case of new onset T2DM in the setting of HR-positive, HER-2 negative breast cancer effectively treated with metformin. Future studies are needed to establish the prevalence and incidence of drug-induced hyperglycemia in patients administered PI3K inhibitors, as well as the best management approach to ensuing hyperglycemia. Reference: André F, Ciruelos EM, Rubovszky G, et.al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940.Guena, E, Roda, D, Rafii, S. Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on phase I clinical trials. Br J Cancer. 2015;113:1541-1547Busaidy, NL, Farooki, A, Dowlati, A. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol. 2012;30:2919-2928.