Article Dans Une Revue JHEP Reports Innovation in Hepatology Année : 2024

CDK4/6 inhibitor-induced liver injury: Clinical phenotypes and role of corticosteroid treatment

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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 (Réseau Francophone pour l’étude de l’HEpatotoxicité des Produits de Santé) 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.
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hal-04960494 , version 1 (21-02-2025)

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Lucy Meunier, Eleonora de Martin, Bénédicte Delire, Wiliam Jacot, Séverine Guiu, et al.. CDK4/6 inhibitor-induced liver injury: Clinical phenotypes and role of corticosteroid treatment. JHEP Reports Innovation in Hepatology, 2024, 6 (7), pp.101098. ⟨10.1016/j.jhepr.2024.101098⟩. ⟨hal-04960494⟩
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