CDK4/6 Inhibitor–Associated Drug-Induced Liver Injury: Clinical Characteristics, Management, and Rechallenge Outcomes—A Systematic Review

CDK4/6 inhibitor–associated drug-induced liver injury (DILI) is an uncommon but clinically important adverse event that may necessitate treatment interruption or discontinuation.This study aimed to systematically characterizethe clinical features, management, and rechallenge outcomes of CDK4/6 inhibitor–associated DILI through a pooled analysis of reported cases. Literature was retrieved from PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Chinese Science and Technology Journal Database, J-STAGE, and relevant conference sources, and patient characteristics, biochemical findings, treatment patterns, and outcomes were systematically extracted and analyzed. A total of 62 patients from 37 eligible studies were included. Ribociclib was the most frequently implicated agent (56.5%), followed by abemaciclib (32.3%). The median time to DILI onset was 57 days (IQR 29–74), and 98.2% of patients with available grading data developed grade 3 or higher liver injury. Despite the severity of reported cases, 90.3% of patients recovered. Among 39 patients with clearly reported rechallenge outcomes, recurrent DILI occurred in 41.0%. Recurrence was substantially more frequent after same-drug rechallenge than after switching to an alternative CDK4/6 inhibitor (81.3% vs. 13.0%, p<0.001), whereas no baseline clinical or biochemical variables were significantly associated with DILI recurrence in the exploratory analyses.Overall, CDK4/6 inhibitor–associated DILI can be clinically severe but is frequently reversible after drug withdrawal. Switching to an alternative CDK4/6 inhibitor after complete recovery may represent a potential management strategy in selected patients, although further prospective studies are required to evaluate the safety of this strategy.