ODP257 Alpelisib Treatment Associated With Severe Diabetic Ketoacidosis in a Patient With Metastatic Breast Cancer
Authors: Aziz Shima , Katwal Dilasha , James Deirdre 
Published: November 2022

Abstract

Introduction
Alpelisib is an inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) which was approved by US FDA to treat postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer. PIK3CA signaling is important for the metabolic actions of insulin and inhibition of PIK3CA was associated with hyperglycemia and rarely, ketoacidosis.

Case Presentation
An 82-year-old female patient with medical issues of metastatic breast cancer with recent progression started on Alpelisib one month before presentation. The patient was brought to the emergency department due to altered mental status and seizure on the same day of the presentation. She was tachycardic to 141 beats per minute and tachypneic to 22 breaths per minute. Physical exam was significant for encephalopathy and a right firm and indurated breast. Initial lab tests revealed leukocytosis to 13.1K/ uL, Blood glucose: 1124 mg/dl, Bicarbonate: 13, anion gap of 45, positive urine ketones, calculated Serum Osmolality: 386 mOsm/kg, HbA1c: 9.1, elevated corrected sodium to 147 mEq/L and elevated creatinine to 3.26 mg/dl from baseline of 0.61 mg/dl. Brain imaging including CT, MRI and MRA without acute findings. Infectious and ischemic workup were negative. She was admitted to neurocritical care as a case of new onset status epilepticus and new-onset diabetes complicated by severe Diabetic Ketoacidosis (DKA) treated with intravenous insulin drip, intravenous fluids and electrolytes replacement. During her admission, Alpelisib was held. The patient improved during the course of hospitalization with resolution of encephalopathy and ketoacidosis by the second day of hospitalization. She was transitioned from insulin infusion to multiple subcutaneous daily insulin regimen and her blood glucose readings remained controlled. Her oncologist was following and decided to stop Alpelisib and to proceed with palliative treatment until further evaluation as an outpatient. Patient was discharged home on multiple daily insulin regimen with outpatient follow ups with endocrinology and oncology.

Discussion
PIK3CA is the most commonly mutated gene in HR+/HER2- advanced or metastatic breast cancer and it is an indicator of poor prognosis. PIK3CA signaling is also important for the metabolic actions of insulin. Alpelisib is an inhibitor of PIK3CA. The SOLAR-1 trial, a phase 3 randomized clinical trial, showed significantly prolonged progression- free survival in patients whose tumors had a PIK3CA mutation treated with Alpelisib. However, hyperglycemia including severe ketoacidosis were also noted. Hyperglycemia was reported in 65% and ketoacidosis was reported in 0.7% of patients treated with Alpelisib. Alpelisib-induced DKA is a rare, but life-threatening, adverse event. There have been few reported cases in the literature. We want to emphasize the importance of screening, monitoring and intensifying treatment of patients with hyperglycemia who are on Alpelisib treatment.
Presentation: No date and time listed