(270) Unraveling Capivasertib: A Critical Paradox of Diabetic Ketoacidosis in Nondiabetic Breast Cancer

Introduction: Immunotherapy has revolutionized cancer treatment but carries notable side effects. This report examines a severe case of refractory diabetic ketoacidosis (DKA) triggered by Capivasertib, a novel therapy for breast cancer.

Description: An 82-year-old female with a history of coronary artery disease, heart failure (EF 30-35%), and breast cancer treated with Faslodex and Capivasertib presented with two days of weakness, decreased appetite, and vomiting. She recently had uncomplicated cystitis treated with Macrobid.
In the emergency department, she was diagnosed with mild DKA. Her EKG showed T-wave inversion in several leads and elevated troponins, suggesting a non-ST-elevation myocardial infarction (NSTEMI). Immediate management included fluid resuscitation, insulin, heparin infusion, and broad-spectrum antibiotics. As her blood pressure dropped, she was moved to the ICU.
In the ICU, her condition worsened. Repeated EKGs showed worsening ST depressions, and troponin levels kept rising. Despite increasing insulin to 17 units/kg/hr, her metabolic state did not improve, with pH of 7.06, an anion gap above 29 mmol/L, beta-hydroxybutyrate increasing to 9.74 mmol/L, glucose levels over 1000 mg/dL, and hyperkalemia with potassium levels over 6 meq/L. Additional fluids were also administered.
Her mental status declined, requiring intubation. She needed four vasopressors to maintain blood pressure. Given her critical condition, her family decided to shift to comfort care.

Discussion: Capivasertib, a selective ATP-competitive pan-AKT kinase inhibitor targeting AKT1, AKT2, and AKT3, is used for hormone receptor-positive, HER2-negative breast cancer, often with fulvestrant. FDA data shows DKA and diabetic metabolic decompensation incidences of 0.3% and 0.6%, respectively. The median onset of hyperglycemia is 15 days, aligning with the start of Capivasertib in this case.
This case highlights the need for vigilance when prescribing Capivasertib, especially in patients with cardiovascular comorbidities and advanced age. Although severe side effects are rare, they can cause significant morbidity, particularly DKA, which can worsen existing cardiac conditions. Therefore, rigorous blood glucose monitoring is essential for patients on Capivasertib.