MON-255 - Capivasertib-Induced Hyperglycemia in A Patient with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Metastatic Breast Cancer and No Prior History of Diabetes Mellitus: A Case Report

Introduction:
Capivasertib, a selective AKT inhibitor approved in combination with fulvestrant for estrogen receptor–positive, HER2-negative advanced breast cancer with PI3K/AKT pathway alterations, is associated with metabolic adverse effects, most notably hyperglycemia. Although patients with poorly controlled diabetes were excluded from pivotal trials, severe hyperglycemia has been reported even in individuals without pre-existing glucose intolerance.

Case:
We report the case of a 55-year-old woman with advanced breast cancer and no prior history of diabetes mellitus (HbA1c 5.52%) who developed grade 4 hyperglycemia four days after initiation of Capivasertib. She presented with progressive generalized weakness and polydipsia, with capillary blood glucose levels persistently ranging from 508 to 574 mg/dL, refractory to initial subcutaneous insulin therapy. Management required continuous intravenous insulin infusion and temporary discontinuation of Capivasertib. Following glycemic stabilization, Capivasertib was successfully reintroduced at a reduced dose with concomitant basal insulin, achieving adequate glycemic control without recurrence of severe hyperglycemia.

Discussion:
This case highlights the potential for rapid-onset, severe hyperglycemia associated with Capivasertib, even in patients with normal baseline glucose metabolism. The presentation and course are consistent with previously reported cases and reflect an on-target metabolic effect of AKT inhibition leading to insulin resistance. Early recognition, prompt insulin therapy, and individualized dose adjustment allowed safe continuation of oncologic treatment.

Keywords:
Capivasertib; hyperglycemia; AKT inhibitor; breast cancer; insulin resistance; adverse drug reaction

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