Ketoacidosis in a Patient with Type 2 Diabetes Requiring Alpelisib: Learnings and Observations Regarding Alpelisib Initiation and Rechallenge

BACKGROUND: Diabetic ketoacidosis (DKA) is a rare complication of alpelisib, but cases of DKA are reported. Alpelisib's safety in patients with long-standing, suboptimally controlled diabetes is unclear since clinical trials of alpelisib did not include them. CASE: A case is presented on a patient with metastatic breast cancer and type 2 diabetes admitted for DKA eleven days after starting alpelisib. Since DKA is implicated in antihyperglycemics that inhibit sodium-glucose cotransporter-2 (SGLT2) inhibitors, her empagliflozin was discontinued. Alpelisib was also held since it was recently initiated. After the DKA resolved, she was discharged and restarted alpelisib. Within 4 hours of taking the first dose, the patient developed a second episode of DKA, and alpelisib treatment was stopped permanently. CONCLUSION: Patients with long-standing type 2 diabetes are at high risk of alpelisib-induced Grade 3 and 4 hyperglycemia, including DKA. It is essential to communicate with non-oncology stakeholders about the risk of DKA with alpelisib as it can be overlooked for more common causes. Restarting alpelisib can result in severe hyperglycemia or DKA within 24 hours of the first dose. In this population, the risks associated with rechallenging alpelisib must be heavily weighed against its benefits. Before restarting alpelisib, a thorough evaluation of the appropriateness of the patient’s antihyperglycemics and diet must occur to anticipate and mitigate a second event. Antihyperglycemics independent of the PI3K/AKT/mTOR pathway may be preferred agents. A plan should be in place to quickly respond to rising glycemia and early referral to a diabetologist or endocrinologist is recommended. Continuous glucose monitoring and hospital admission are recommended during rechallenge. A better understanding of alpelisib-induced hyperglycemia, especially in patients with diabetes, is required to navigate alpelisib treatment safely. Emphasis should be placed on patient education of symptoms and monitoring parameters.