Case Report: Diabetic ketoacidosis following EGFR-TKIs therapy via aggravated insulin resistance.

OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an established first-line treatment for non-small cell lung cancer (NSCLC) patients with sensitizing mutations because of their remarkable efficacy and favorable tolerability profiles. However, rare and severe adverse reactions during their application require attention. Cases of diabetic ketoacidosis (DKA) associated with EGFR-TKI therapy have seldom been reported and the underlying mechanism remains unclear. CASE PRESENTATION: We present the case of a 64-year-old female patient with immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) on aumolertinib (a third-generation EGFR-TKI, 110 mg daily) for the treatment of NSCLC admitted to the hospital with frequent episodes of DKA. Owing to a recurrent DKA episode following a reduced dosage (55 mg daily), aumolertinib was suspended permanently. After full recovery from the DKA, the patient was switched to osimertinib (80 mg daily). Insulin resistance in the patient was assessed using a hyperinsulinemic-euglycemic clamp. She was maintained on standard-dose osimertinib and insulin therapy after discharge and remained asymptomatic during the outpatient follow-up. CONCLUSION: Owing to the protocol-defined strict inclusion and exclusion criteria, some potentially serious adverse reactions may not be as commonly observed in clinical trial settings. Aumolertinib-induced exacerbation of insulin resistance can precipitate a spectrum of hyperglycemia, ranging from mild elevations to severe DKA, which highlights the necessity of blood glucose monitoring throughout the treatment course. By assessing a patient's tolerance profile for EGFR-TKIs-aggravated insulin resistance using the insulin clamp technique, clinicians can optimize antineoplastic regimens, such as switching from aumolertinib to osimertinib in this case.