Alpelisib-Induced Diabetic Ketoacidosis- A Case Report

Abstract

Background: Alpelisib, in combination with Fulvestrant, was approved in 2019 by the Food and Drug Administration for treatment of HR+, HER2- advanced or metastatic breast cancer in patients with PIK3CA mutation. a This combination is currently on phase III of study. One of the most common side effects is hyperglycemia. Rarely, this can be severe enough to induce diabetes ketoacidosis, which is an indication for interrupting Alpelisib treatment.

Clinical Case: A 78 year old female presented to our emergency department with altered mentation. Her past medical history is significant for metastatic breast cancer, with known PIK3CA mutation, started on alpelisib three months prior. Concomitantly, despite not carrying a diagnosis of diabetes mellitus, the patient was started on metformin, due to the known side effect of hyperglycemia. Upon admission, the patient was found to be tachycardic and otherwise hemodynamically stable. Pertinent laboratory studies revealed an initial serum glucose of 600 (nl 70–100) mg/dL, potassium of 5.4 (nl 3.5–5.1) mmol/L, serum carbon dioxide of 8 (nl 21–32) mmol/L, calculated anion gap of 25 (nl <12) mEq/L, and a serum beta-hydroxybutyrate > 4.50(nl 0.02–0.27) mmol/l. ABG revealed a pH of 7.11, PaO2 of 102, pCO2 of 11, and a lactate of 4.0 mmol/L. Glycated hemoglobin was 10.7% (nl <6.5%). EKG revealed sinus tachycardia with PACs, abnormal anterolateral T wave inversion, and a QTc of 519 msec. Initial troponin was elevated at 0.15 with a max troponin at 1.40 ng/mL. Urinalysis revealed glucosuria. Chest x-ray showed no acute cardiopulmonary process. Blood cultures were negative to completion. Patient was admitted for diabetic ketoacidosis and was started on DKA protocol which included aggressive hydration with sodium chloride and insulin drip. Alpelisib was discontinued immediately. Upon resolution of the anion gap metabolic acidosis, the patient’s encephalopathy significantly improved. She was transitioned to subcutaneous insulin. During the same hospitalization, the patient’s serum glucose rapidly normalized and she did not require insulin at the time of discharge.

Conclusion: Diabetic ketoacidosis is an unusual but life-threatening side effect of Alpelisib, even in patients without an underlying diagnosis of diabetes mellitus. This case suggests that such patients should have a close monitoring of glycemic control and intensification of their anti-diabetic medications if required, to prevent hyperglycemic crises.