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

Background

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.

Methods

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.

Results

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: 473P

Baseline characteristics of cases and control

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

VHIO.

Funding

Has not received any funding.

Disclosure

C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, SeaGen, Zymeworks, Genentech, Innoup, Millenium, Pharmalex Spain SLU; Financial Interests, Personal, Other, SC: Byondis B.V., Glaxo, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La RocheLtd, Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). M. Bellet Ezquerra: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Lilly, Stemline-Menarini; Other, Speaker's Bureau and Travel Expenses: Pfizer; Other, Speaker's Bureau: Novartis, Lilly. All other authors have declared no conflicts of interest.