SAT-524 Managing Capivasertib Induced Hyperglycemia in a Patient with Pre-Existing Type 2 Diabetes

Abstract Disclosure: K. Cuan: None. J. Samavedam: None. A. Lee: None. B.Y. Wong: None. Background: The treatment of breast cancer has increasingly focused on targeting the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Hyperglycemia is a frequent adverse event associated with PI3K inhibitors. The AKT inhibitor, capivasertib, has been approved by the US Food and Drug Administration (FDA) in combination with fulvestrant in the treatment of HR+, HER2- breast cancer. AKT-induced hyperglycemia is also a significant adverse event. We present a case of capivasertib use in a patient with pre-existing type 2 diabetes that was managed on metformin and pioglitazone. Clinical Case: A 71-year-old woman with class I obesity, type 2 diabetes, and metastatic ER+/PR+/HER2- breast cancer with osseous metastases and PIK3CA mutation, was started on alpelisib. She was not on diabetes medications prior to alpelisib with HbA1c 7.3 µmol/L (4.7-6.4 µmol/L). After starting alpelisib, her hyperglycemia worsened with HbA1c peaking at 9.1 µmol/L. Alpelisib was held for grade 3 hyperglycemia and resumed at a lower dose. Metformin 1000 mg twice daily and pioglitazone 15 mg daily were started. Glycemic control was difficult to assess due to inconsistent alpelisib use from nausea and vomiting. Alpelisib was stopped following progression of breast cancer. Capivasertib 320 mg twice daily for 4 days a week was started several months later. Pioglitazone was preemptively increased to 30 mg daily and metformin was continued at 1000 mg twice daily. A 2-week CGM trial after starting capivasertib showed TIR 95%. Capivasertib was adjusted from 320 to 400 mg twice daily. Labs showed HbA1c 6.2 µmol/L, c-peptide 2.43 ng/mL (1-4 ng/mL), serum insulin 5.7 uU/mL (<20 uU/mL), and serum glucose 82 mg/dL (70-140 mg/dL). Due to hormone receptor status change, capivasertib was stopped 2 months later. Conclusion: Therapeutic agents that target the PI3K/AKT/mTOR signaling pathway are increasingly common in breast cancer treatment. Hyperglycemia is prevalent with aleplisib, the first FDA approved PI3K inhibitor, occurring in 64% of patients in the SOLAR-1 trial. While management of PI3K inhibitor associated hyperglycemia remains under investigation, low carbohydrate diets and oral antiglycemic agents have been reported. AKT inhibitors, targeting the same signaling pathway, also cause hyperglycemia. In the CAPItello-291 trial, hyperglycemia was observed in 16.3% of patients treated with capivasertib-fulvestrant, of which 2.3% were grade 3 hyperglycemia. The intermittent administration schedule of capivasertib may explain its lower incidence of hyperglycemia compared to aleplisib. Strategies for prevention and management of AKT inhibitor associated hyperglycemia are not well established. Our case highlights the successful use of metformin and pioglitazone to manage capivasertib induced hyperglycemia in a patient with pre-existing type 2 diabetes. Presentation: Saturday, July 12, 2025