MON-620 - Unmasking A Rare Adverse Effect: Capivasertib-Induced Diabetic Ketoacidosis

Introduction
We present a case of capivasertib-induced diabetic ketoacidosis, which is an exceedingly rare adverse event.

Case presentation
A 75-year-old woman with metastatic breast cancer and no prior history of diabetes presented with generalized weakness and confusion. She had started capivasertib 2 days prior to admission. On presentation, she had blood glucose of 604 mg/dL, pH 7.08, CO2 15 mmol/L, anion gap 19 mmol/L, and ketonuria. HbA1c 1 week before admission was 4.4% with serum glucose 92 mg/dL. Endocrinology was consulted, and she was admitted to the ICU for initiation of insulin drip. She required exceedingly high amounts of insulin up to 49 units/hour.
She was intubated due to worsening hypoxic respiratory failure and required dual vasopressors for severe hypotension. The clinical course was further complicated by acute kidney injury. Patient was unable to participate in medical decisions because of altered mental status. Due to the patient's deteriorating clinical condition, her family opted not to pursue invasive interventions and elected comfort care, and she passed away.

Discussion
Capivasertib is a novel oral pan-AKT kinase inhibitor approved for treatment of hormone receptor-positive, HER2-negative breast cancer. Capivasertib-induced hyperglycemia results from AKT-inhibition, disrupting the PI3K-AKT pathway, thus impairing insulin-mediated glucose uptake and increasing hepatic glucose production, leading to insulin resistance and hyperglycemia.
Diabetic ketoacidosis is reported only in 0.3% of patients on capivasertib. Although rare, capivasertib-induced DKA is a potentially fatal side effect.
The manufacturer recommends routine laboratory monitoring of fasting blood glucose on Day 3 or 4 of the dosing weeks initially and then monthly while on treatment. Waiting until day 3 or 4 to monitor fasting blood glucose could delay prompt recognition of rapidly progressive capivasertib-induced severe hyperglycemia.
Our patient did not have obesity and HbA1C was normal at 4.4%. This case highlights the need to assess other predictors of severe hyperglycemia because HbA1c and elevated body mass index alone could potentially underestimate the risk.

Conclusion
The clinical implication of our case report is that capivasertib-induced severe hyperglycemia can occur even in the absence of known risk factors. This case highlights the need to reassess the recommended time for glycemic monitoring and for further research to identify other predictors of capivasertib-induced hyperglycemia.

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