473P Predictive factors for drug-induced liver injury in patients with ER-positive HER2-negative metastatic breast cancer treated with first-line cyclin-dependent kinase 4/6 inhibitors

The combination of endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDKi) for ER+HER2neg metastatic breast cancer has been associated with 13% of drug-induced liver injury (DILI). In a previous work (Vega et al, ESMO Breast 2023), we identified 26 cases of DILI (5.5%), defined as AST/ALT elevation ≥G2, among 472 patients (pts) treated. Here, we present a case-control study to evaluate the clinical factors associated with DILI. The case-control study includes i) 89 pts without DILI randomly selected and retrospectively analyzed (control group) and ii) 26 cases with DILI previously reported. 15 potential predictive factors were evaluated either individually or in combination. Baseline liver steatosis was based on computed tomography reports. To study the association with DILI, odds ratios (ORs) were calculated using logistic regression. The main characteristics of the 115 pts are shown in the table. In the univariate analysis, no baseline risk factor alone was statistically associated with DILI, steatosis and AST/ALT baseline elevation had the best results (p<0.15). However, the combination of steatosis and pre-menopause status (n=9, 7.8%) significantly increased the risk to 66.7% vs 19% (20/105) (OR=8.6, 95% CI 2.1-43.6; p=0.004). No other variables, including cardiovascular risk factors, ET partner or liver metastasis predicted DILI development. Table: 473PBaseline characteristics of cases and controlCases n=26Controls n=89Palbociclib832Abemaciclib929Ribociclib928Age (median)6160Overweight33%36%Obesity26%28%Pre-Menopause54%35%Hypertension27%27%Diabetes mellitus4%11%Dyslipidemia31%29%Aromatase inhibitor65%57%Fulvestrant35%43%Liver metastasis27%30%Steatosis31%15%Baseline ALT or AST >35 IU/mL36%17% Open table in a new tab In our case-control series, the combination of premenopausal status and steatosis was the strongest predictor for CDKi-related DILI. Our findings suggest that metabolic changes due to ovarian factor suppression cooperate with CDKi to induce DILI in pts with underlying steatosis. A prospective study is needed to validate these findings.