Risk factors of hepatotoxicity with ribociclib in hormone receptor-positive breast cancer

BACKGROUND: The standard first-line treatment for hormone receptor-positive metastatic breast cancer is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, including palbociclib, ribociclib, or abemaciclib, combined with endocrine therapy. Hepatobiliary toxicity is an important adverse effect of ribociclib. This study compared the risk of hepatotoxicity between ribociclib and palbociclib and identified factors associated with hepatotoxicity. METHODS: This retrospective cohort study included patients with hormone receptor-positive breast cancer receiving ribociclib or palbociclib between January 1, 2018 and June 1, 2022. Hepatotoxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, with grade 2 or higher considered as the study outcome. Kaplan-Meier analysis assessed time to hepatotoxicity, and a multivariable Cox proportional hazards model estimated adjusted hazard ratios. RESULTS: The mean age was 61 years, and all patients were women. Among 145 patients receiving ribociclib, 28 developed hepatotoxicity, compared with 19 of 153 patients receiving palbociclib. The median time to hepatotoxicity was 42 days in both groups. After adjustment for age, Charlson Comorbidity Index (CCI) score, history of hepatitis B virus (HBV) infection, fatty liver, and liver metastasis, the adjusted hazard ratio (HR) for palbociclib compared with ribociclib was 0.467 (95% confidence interval [CI], 0.233-0.936; p = 0.0320). In the overall population, liver metastasis (HR, 2.159; 95% CI, 1.175-3.966; p = 0.0131), history of HBV infection (HR, 2.216; 95% CI, 1.102-4.458; p = 0.0256), and fatty liver (HR, 3.536; 95% CI, 1.840-6.794; p = 0.0002) were associated with higher risk of hepatotoxicity. CONCLUSION: Compared with palbociclib, ribociclib was associated with a higher risk of hepatotoxicity during the first six months of treatment. Closer monitoring of liver function may be warranted, particularly in patients with liver metastases, a history of HBV infection, or fatty liver who receive ribociclib.