■细胞周期蛋白依赖性激酶4/6(CDK4/6)抑制剂是激素受体阳性患者全身治疗的基石,HER2阴性(HR+/HER2-)转移性乳腺癌。在CDK4/6抑制剂的各种治疗研究中,肝脏检查中的升高比对照组更频繁。CDK4/6抑制剂诱导的肝毒性机制尚不清楚;自然史和适当的管理描述不佳。
■我们进行了一项回顾性研究,从REFHEPS数据库收集CDK4/6肝炎病例(RéseauFranophonepourl'étakedel'HepatotoxicitédesProduitsdeSanté)。
■在这项研究中,我们报告了22例CDK4/6抑制剂(ribociclib,n=19和abemaciclib,n=3)。根据CTCAE分类,所有肝炎病例均为3级或4级.12例(54.6%)患者的肝活检显示急性中央型肝炎,伴有坏死灶和淋巴细胞浸润。9例(40.9%)患者接受了皮质类固醇治疗以解决肝炎。在三种情况下,另一种CDK4/6抑制剂可以在肝炎消退后恢复治疗而不复发.
■CDK4/6抑制剂诱导的肝炎在文献中描述不充分,但有几个论点指出,这些药物应包括在DI-ALH(药物诱导的自身免疫样肝炎)类别。
■这项研究强调了CDK4/6抑制剂的临床意义和肝毒性风险,比如ribociclib和abemaciclib,在HR+/HER2转移性乳腺癌治疗中。它强调了加强肝脏监测和量身定制的管理策略的必要性,包括对停药后未解决的肝炎进行皮质类固醇干预。这些发现对肿瘤学家至关重要,肝病学家,和病人,指导治疗决策,并在治疗期间指示仔细肝功能监测。糖皮质激素在治疗药物性肝炎中的应用以及恢复后恢复CDK4/6抑制剂治疗的可行性是显着的实际结果。尽管如此,研究的回顾性性质和有限的病例数引入了限制,强调需要进一步研究以完善我们对CDK4/6抑制剂相关肝毒性的理解.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: This study highlights the clinical significance and hepatotoxic risks of CDK4/6 inhibitors, like ribociclib and abemaciclib, in HR+/HER2-metastatic breast cancer treatment. It underscores the necessity for enhanced hepatic monitoring and tailored management strategies, including corticosteroid intervention for unresolved hepatitis post-withdrawal. These findings are crucial for oncologists, hepatologists, and patients, guiding therapeutic decisions and indicating careful liver function monitoring during therapy. The utility of
corticosteroids in managing drug-induced hepatitis and the feasibility of resuming CDK4/6 inhibitor therapy post-recovery are notable practical outcomes. Nonetheless, the study\'s retrospective nature and limited case numbers introduce constraints, underscoring the need for further research to refine our understanding of CDK4/6 inhibitor-associated hepatotoxicity.