Introduction: Capivasertib (Truqap) was FDA-approved in 2023 for the treatment of breast cancer. The dosing is 400mg twice daily for four days then off for three days. It has several known side effects, including hyperglycemia and diabetic ketoacidosis. However, there have only been a few cases previously described in the literature, of which the majority result in patient mortality. Description: A 59-year-old female with metastatic breast cancer was started capivasertib and experienced a tonic clonic seizure. The patient erroneously received 400mg twice daily for six days consecutively prior to the event. On admission, she had a blood glucose level >1200 mg/dL, pH 7.08, beta-hydroxybutyrate of 2.20mmol/L, and anion gap 18. The patient had no history of diabetes with A1c 5.6%. She was admitted to the ICU where she was intubated, started on continuous EEG and antiseizure medications, vasopressor infusions, and intravenous insulin. She experienced refractory hyperglycemia and required up to 48 units/hour of insulin. Her blood glucose values were unmeasurably high, and measurement of blood glucose was done using a 1:1 dilution of blood and normal saline and multiplied by two. Titration of the insulin infusion was directed by the care team, as opposed to EndoTool®, with a goal to decrease blood glucose by 100 mg/dL/hr and avoid cerebral edema. CT head was negative on admission and repeat scan at 48 hours was also negative. After 48 hours, blood glucose values downtrended, the anion gap closed, and the patient was transitioned from intravenous insulin to a subcutaneous regimen. She was eventually liberated from the ventilator, transferred to the floor, and discharged home. Capivasertib was not restarted. Discussion: Capivasertib inhibits protein kinase B. Normally, this protein plays a role in the pathway that helps cancer cells avoid cell death, and therefore inhibition leads to cancer cell death. Consequences of this inhibition via capivasertib have significant downstream effects in normal cells. These include altered regulation of blood glucose as protein kinase B promotes glycogen storage and facilitates glucose uptake into the tissues. Although reports of life-threatening hyperglycemia are rare, it is important for clinicians to recognize the risks in patients with and without diabetes.
Mitchell et al. (Sun,) studied this question.