Wong Wilfrid H F, Vasiliu Simona, McFarlane Thomas
School of Pharmacy, Faculty of Science, University of Waterloo, Kitchener, Canada.
Odette Cancer Centre, Sunnybrook Health Sciences, Toronto, Canada.
Support Care Cancer. 2025 Jun 16;33(7):588. doi: 10.1007/s00520-025-09625-0.
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become key agents in the treatment of hormone receptor positive (HR +), human epidermal factor receptor 2 negative (HER2-) metastatic breast cancer (MBC). In combination with endocrine therapy, CDK4/6 inhibitors are currently considered first-line treatment for HR + /HER2- MBC. There are three CDK4/6 inhibitors currently available: palbociclib, ribociclib and abemaciclib. The toxicity profiles of the CDK4/6 inhibitors are well-detailed in the respective clinical trials and post-marketing reports. This review will detail the hepatotoxic effects of CDK 4/6 inhibitors and how the incidence rate compares among agents.
This narrative review will fulfill the following objectives: 1. Record and analyze the rates of palbociclib, ribociclib and abemaciclib induced hepatotoxicity in HR + /HER2- breast cancer patients in the literature. 2. Compare the incidences of hepatotoxicity between ribociclib, abemaciclib and palbociclib. 3. Summarize findings and outline future directions in research.
Databases (PubMed, Embase) were searched on January 24, 2024.
Evaluating the systematic reviews and meta-analyses included in the narrative review, ribociclib showed the highest risk for all-grade (AG) and grade ≥ 3 (G3 +) alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) elevation. Additionally, ribociclib showed the highest incidence rate of AG and G3 + ALAT/ASAT elevation across its respective randomized clinical trials (RCTs) and pooled safety analysis. Palbociclib showed the highest incidence rate of AG ALAT/ASAT elevation in its respective RCTs and pooled safety analysis. However, palbociclib showed the lowest risk for both AG and G3 + ALAT/ASAT elevation.
Twenty-five systematic reviews and meta-analyses, RCTs, pooled safety analysis and observational studies were included in this narrative review to evaluate the incidence rate of palbociclib, ribociclib and abemaciclib induced hepatoxicity. Ribociclib seems to be associated with the highest risk of drug-induced hepatotoxicity. More studies need to be done to confirm and quantify this finding.
细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂已成为激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）转移性乳腺癌（MBC）治疗的关键药物。与内分泌治疗联合使用时，CDK4/6抑制剂目前被认为是HR+/HER2-MBC的一线治疗方案。目前有三种CDK4/6抑制剂：哌柏西利、瑞博西尼和阿贝西利。CDK4/6抑制剂的毒性特征在各自的临床试验和上市后报告中有详细描述。本综述将详细阐述CDK4/6抑制剂的肝毒性作用以及各药物之间的发生率比较情况。
本叙述性综述将实现以下目标：1.记录并分析文献中哌柏西利、瑞博西尼和阿贝西利在HR+/HER2-乳腺癌患者中引起肝毒性的发生率。2.比较瑞博西尼、阿贝西利和哌柏西利之间肝毒性的发生率。3.总结研究结果并概述未来的研究方向。
于2024年1月24日检索了数据库（PubMed、Embase）。
评估本叙述性综述中纳入的系统评价和荟萃分析，瑞博西尼在所有级别（AG）和≥3级（G3+）丙氨酸氨基转移酶（ALAT）和天冬氨酸氨基转移酶（ASAT）升高方面显示出最高风险。此外，在其各自的随机临床试验（RCT）和汇总安全性分析中，瑞博西尼的AG和G3+ALAT/ASAT升高发生率最高。哌柏西利在其各自的RCT和汇总安全性分析中，AG ALAT/ASAT升高发生率最高。然而，哌柏西利在AG和G3+ALAT/ASAT升高方面的风险最低。
本叙述性综述纳入了25项系统评价和荟萃分析、RCT、汇总安全性分析和观察性研究，以评估哌柏西利、瑞博西尼和阿贝西利引起肝毒性的发生率。瑞博西尼似乎与药物性肝毒性的最高风险相关。需要进行更多研究来证实和量化这一发现。
