1875P - Real-world evidence of ribociclib induced liver toxicity in patients with breast cancer: A multi-center experience

Background

CDK4/6 inhibitors are primarily used to treat hormone-positive metastatic breast cancer. Although ribociclib is generally well tolerated, some common side effects may occur, including hepatotoxicity, hypertension, neutropenia, diarrhea, QTc interval prolongation, and infections. However, there is limited real-world data about hepatotoxicity associated with using ribociclib. Therefore, we evaluated the characteristics and management of ribociclib-related hepatotoxicity.

Methods

Patients who had received ribociclib in a metastatic setting screened between 2019 and 2023 and patients who had liver toxicity were included. There were no other exclusion criteria.

Results

A total of 845 patients were screened, and 78 (9.2%) were found to have developed liver toxicity. Of these, 5 (0.6%) had grade 4 toxicity, 19 (2.2%) had grade 3, and 54 (6.4%) had grade 1-2 toxicity. In patients with grade 4 toxicity, ribociclib was discontinued (one of whom was successfully re-challenged with ribociclib), and 2 (0.2%) patients needed a liver biopsy (one of whom was diagnosed with drug-induced autoimmune hepatitis). In patients with grade 3 toxicity, dose reduction was applied in 11 (1.3%) patients, and ribociclib was stopped in 5 (0.6%) patients. For patients with grade 1-2 toxicity, dose reduction was applied in 7 (0.8%) patients, and only 1 (0.1%) patient permanently discontinued ribociclib. No fatal case of hepatotoxicity has been reported. The median time from the initiation of ribociclib to the onset of liver toxicity was 13 weeks. The median time from the initiation of ribociclib to the final follow-up was 16 months. In multivariate analysis (age, liver metastasis, stage diagnosis), patients with grade 3-4 hepatotoxicity had decreased OS compared to patients with grade 1-2 hepatotoxicity (HR: 2.7, 95% CI 1.01-7.11, p=0.047).

Conclusions

Ribociclib is associated with an increased risk of hepatotoxicity, with the potential for grade 3-4 in a small number of patients. This study also demonstrated a relationship between ribociclib-related hepatotoxicity and overall survival. Regular monitoring of liver function tests during ribociclib treatment may help clinicians identify high-risk patients requiring closer follow-up.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.