CDK4/6 Inhibitor-Induced Liver Injury: Clinical Phenotypes and Role of Corticosteroid Treatment

Background & Aims: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are the cornerstone of systemic therapy for patients with hormone receptor -positive, HER2-negative (HR+/HER2-) metastatic breast cancer. In the various therapeutic studies with CDK4/6 inhibitors, elevations in liver tests were more frequent than in the control groups. The mechanism of CDK4/6 inhibitor -induced liver toxicity is not well understood; moreover, natural history and appropriate management are poorly described. Methods: We conducted a retrospective study, collecting cases of CDK4/6 hepatitis from the REFHEPS (R & eacute;seau Francophone pour l'& eacute;tude de l'HEpatotoxicit & eacute; des Produits de Sant & eacute;) database. Results: In this study, we report on 22 cases of hepatitis induced by CDK4/6 inhibitors (ribociclib, n = 19 and abemaciclib, n = 3). According to the CTCAE classification, all hepatitis cases were grade 3 or 4. Twelve (54.6%) patients had a liver biopsy showing acute centrilobular hepatitis with foci of necrosis and lymphocytic infiltrate. Nine (40.9%) patients were treated with corticosteroids for resolution of hepatitis. In three cases, another CDK4/6 inhibitor could be resumed after resolution of the hepatitis without recurrence. Conclusions: CDK4/6 inhibitor -induced hepatitis is poorly described in the literature but there are several arguments pointing out that these drugs should be included in the DI-ALH (drug -induced autoimmune-like hepatitis) category. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).