Alpelisib May Cause Diabetic Ketoacidosis in Patients With Breast Cancer

Patients receiving alpelisib for advanced breast cancer may be at risk of developing diabetic ketoacidosis, according to research published in Clinical Breast Cancer.

Researchers found evidence to suggest that alpelisib can cause diabetic ketoacidosis, which often leads to hospitalization and can be fatal.

For this study, researchers searched the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2019 to 2022, and they calculated the reporting odds ratio of diabetic ketoacidosis events with alpelisib.

There were 6201 reports of adverse events with alpelisib and 6868 reports of diabetic ketoacidosis with any drug. After duplicate reports were removed, there were 87 unique reports of diabetic ketoacidosis that were specific to alpelisib. The reporting odds ratio was 9.84 (95% CI, 7.3-13.2).

The 87 patients with diabetic ketoacidosis had a median age of 64 (range, 34-80) years, although 47% of cases did not have an age reported. Reports were made by a health care professional in 78% of cases and by a consumer in 18% of cases. The majority of the reports (75%) were made in North America.

Most patients with diabetic ketoacidosis (77%) were hospitalized, 15% of patients had life-threatening diabetic ketoacidosis, 2% were disabled by diabetic ketoacidosis, and 13% of patients died from it.

Most patients (n=65) were not receiving concurrent medications. There were 3 cases of concurrent medication use that might have contributed to hyperglycemia, including 1 case of steroid use and 2 cases of mTOR inhibitor use. Three patients were taking antihyperglycemic medication.

As a supplement to the database analysis, the researchers performed a literature review and identified 11 published case studies of diabetic ketoacidosis associated with alpelisib use. Three of the patients had type 2 diabetes, and 2 of these patients were receiving antihyperglycemic medications. Another 3 patients were considered prediabetic.

The patients in the case studies had a starting alpelisib dose of 300 mg twice daily. The median time to onset of diabetic ketoacidosis was 14 days, and all patients recovered. Of 5 patients who underwent alpelisib rechallenge, 2 experienced a recurrence of hyperglycemia or diabetic ketoacidosis and had to discontinue alpelisib.

“To the best of our knowledge, this analysis is the first to utilize a pharmacovigilance database to evaluate an association between alpelisib exposure and a reporting signal for DKA [diabetic ketoacidosis],” the researchers wrote. “Our findings provide a signal on the potential association between alpelisib and DKA. This is an important finding as DKA is considered a medical emergency.”

This article originally appeared on Cancer Therapy Advisor