471P - Liver toxicities during cyclin-dependent kinase inhibitors (CDKi) in patients affected by hormone receptor-positive breast cancer (BC)

Background

CDKi are standard of care for patients (pts) with advanced hormone-positive (HR+) BC, with recent results even in the adjuvant setting. Nevertheless, management and clinical implication of hepatotoxicity during CDKi are not well described in literature, even if it is reported in a non-negligible rate within trials.

Methods

A multicenter Italian retrospective study was conducted in 2023, collecting and pooling data of pts affected by HR+ HER2- BC, treated with CDKi and aromatase inhibitors (AI) or fulvestrant (FULV). This study aims to describe the incidence and the management of liver adverse events (AEs) during CDKi in a real-world setting. A descriptive analysis was performed as pivotal evaluation for designing an observational study.

Results

256 pts were included across 5 centres: 96% of pts received CDKi in the metastatic setting. Pts were treated with ribociclib (42%), abemaciclib (25%) and palbociclib (33%) associated with AI or FULV. Liver AEs occurred in 16% of pts, with a median time of onset of 90 days. 19 pts (46%) experienced grade ≥3 (G≥3) liver AEs: mostly with elevated liver enzymes (95%). No acute liver failure was reported. The rate of liver AEs was 20% for ribociclib, 17% for abemaciclib and 11% for palbociclib. Ribociclib and abemaciclib were associated with 79% and 21% of G≥3 liver AEs. Diagnostic assessments were performed in 37% of pts with liver AEs: hepatotropic viruses screening (68%), autoimmunity screening (28%) and radiological exams (4%). Only one liver biopsy was performed with a diagnosis of drug induced liver injury. Recovery of normal liver function after CDKi discontinuation was achieved in 68% of pts, with a median time of 30 days. After resolution of G≥3 liver AEs, 26% of pts discontinued any treatment, 5% continued only AI or FULV, 48% resumed CDKi with dose reduction and 21% shifted to another CDKi without any further G≥3 liver AEs.

Conclusions

In our cohort the incidence of liver AEs was significant, with a relevant number of G≥3 AEs. Since hepatotoxicity is defined by diagnosis of exclusion, a prompt screening for differential causes is crucial in case of abnormal liver function. After non serious liver AEs, resumption of lower dose or shift to another CDKi may be a safe therapeutic option.

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.