The phosphoinositide 3-kinase (PI3K) pathway is a common target for oncologic therapies and mediates much of insulin’s action. The PI3Kα inhibitor alpelisib is effective in advanced breast cancer but causes hyperglycemia in up to 80% of patients. The FDA label recommends metformin as first-line treatment of alpelisib-induced hyperglycemia. There is no consensus on other options. This is a single-center, retrospective review of new alpelisib users at a cancer center in 2021. Manual chart review for periods of exposure to alpelisib and antidiabetic drugs identified 67 patients newly started on alpelisib. Average age was 59 years. Median exposure time to alpelisib was 103 days. Antidiabetic drugs were prescribed in 48% (32/67) of patients, with 25% (17/67) using 2 or more. Of patients who stopped alpelisib, 14% (5/35) were primarily due to hyperglycemia. Hyperglycemia was a contributing cause in another 3 cases. The only antidiabetic drugs significantly associated with glucose reduction in multivariable analysis were metformin (26 mg/dL reduction, 95% CI 6.4 - 45.6) and SGLT2 inhibitors (74 mg/dL reduction, 95% CI 42 - 104) . Diabetic ketoacidosis (DKA) occurred in 6% (4/67) of patients. There was a higher rate of DKA among SGLT2 inhibitor users compared to nonusers (p=0.019) . SGLT2 inhibitors are effective as second-line to metformin for alpelisib-induced hyperglycemia but with a higher rate of DKA.
M. Weintraub: None. D. Liu: Consultant; Invitae Corporation. J. Flory: None.