Predictors of hepatotoxicity in patients receiving CDK4/6 inhibitors: A real-world cohort study

Abstract

Background

CDK4/6 inhibitors are standard treatments for HR+/HER2– metastatic breast cancer. While effective, hepatotoxicity is a significant clinical concern. This study aimed to evaluate the incidence and clinical predictors of hepatotoxicity in a real-world setting.

Methods

This retrospective study included 70 patients treated with palbociclib or ribociclib between 2020 and 2024. Hepatotoxicity was defined as Grade ≥1 elevation of ALT and/or AST per CTCAE v5.0. Independent predictors were identified using multivariable binary logistic regression, and model performance was assessed via ROC curve analysis.

Results

The mean age was 55.7 ± 10.8 years, and 12.9% had baseline liver metastasis. Hepatotoxicity occurred in 20% (n = 14) of patients. Multivariable analysis identified liver metastasis (OR = 39.3; 95% CI: 4.4–351.9; p = 0.001), hypercholesterolemia (OR = 14.9; 95% CI: 2.0–112.1; p = 0.009), and higher body mass index (OR = 1.19; 95% CI: 1.00–1.41; p = 0.045) as independent predictors. Age and specific CDK4/6 inhibitor type were not significantly associated with toxicity. The predictive model demonstrated strong discriminative ability with an AUC of 0.878.

Conclusions

Hepatotoxicity is common in routine practice. Baseline liver metastasis, hyperlipidemia, and higher BMI are key predictors of risk. These findings suggest that readily available clinical characteristics can identify high-risk patients, supporting the need for individualized liver function monitoring during treatment.