Risk Factors for Abemaciclib-induced Serious Liver Injury in Patients with Hormone Receptor-positive, Human Epidermal Growth Factor Receptor Type 2-negative Metastatic Breast Cancer: A Retrospective Study

Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, is the standard treatment for hormone receptor-positive and human epidermal growth factor receptor type 2 (HER2)-negative inoperable or recurrent breast cancer. The high incidence of hepatic dysfunction is a clinical issue. However, the factors associated with severe liver dysfunction related to drug interruption or discontinuation are unclear. Therefore, we retrospectively investigated risk factors for abemaciclib-induced severe liver dysfunction in female patients with hormone receptor-positive and HER2-negative metastatic breast cancer at the Osaka International Cancer Center from November 2018 to June 2022. Severe liver dysfunction was observed in 18.3％ of patients after the initiation of abemaciclib. Body mass index (BMI; ≥25 kg/m2) before treatment initiation was identified as a risk factor for severe liver dysfunction. Additionally, patients who experienced grade 2 elevations in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) during prior palbociclib administration developed abemaciclib-induced severe liver dysfunction. Therefore, alternative drug treatments should be considered for patients with grade 2 AST/ALT increases who were previously treated with palbociclib. Close monitoring of abemaciclib administration in patients with a BMI of ≥25 kg/m2 will facilitate early detection of severe liver dysfunction and prevent its worsening. For such patients, alternative treatments may be warranted.