Strong Signals of Adverse Events in Tyrosine Kinase Inhibitor Therapy for Liver Cancer Treatment.

IF 2.3 Q3 ONCOLOGY

World Journal of Oncology Pub Date : 2026-01-04 eCollection Date: 2026-04-01 DOI:10.14740/wjon2685

Wen Xuan Zhou, Jun Hao Fan, Qian Wen Ni, Ming Kai Liu, Zhen Peng, Yuan Xu, Su Su Luo

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引用次数: 0

Abstract

Background: This study was to identify strong adverse event (AE) signals associated with four tyrosine kinase inhibitors (TKIs) (sorafenib, regorafenib, lenvatinib, and cabozantinib), and compare these signals with regulatory drug facts from multiple global agencies.

Methods: Data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS, 2007 - 2024) were analyzed. Each AE was treated as a binary variable, and logistic regression with robust error estimation was used to identify strong signals (odds ratio > 2, lower 95% confidence interval > 1). AE signals were compared with drug facts from the FDA (USA), European Medicines Agency (EMA, European Union), Pharmaceuticals and Medical Devices Agency (PMDA, Japan), and National Medical Products Administration (NMPA, China).

Results: Among 33,801 identifiers (137,345 records), 816 strong AE signals were found. Sorafenib had the most (373), followed by regorafenib (207), lenvatinib (126), and cabozantinib (110). Notable AEs included pharyngeal hemorrhage (sorafenib), retinal artery occlusion (regorafenib), intracranial aneurysm (lenvatinib), and mood swings (cabozantinib). Thirty-two signals had a 100% likelihood of critical outcomes, with no overlap across drugs. AEs were more frequent in males and older populations. Significant discrepancies in AE profiles were observed among regulatory agencies, with low overlap between FAERS and agency data.

Conclusions: This study provides a comprehensive analysis of AE signals for four TKIs in liver cancer, identifying associations rather than causal relationships. The findings highlight significant variation in AE profiles and discrepancies between clinical trial data and real-world evidence. These results are hypothesis-generating and emphasize the need for personalized treatments, enhanced monitoring and intervention, and improved global AE reporting, while acknowledging the inherent limitations of spontaneous reporting systems.

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酪氨酸激酶抑制剂治疗肝癌不良事件的强烈信号。

背景：本研究旨在确定四种酪氨酸激酶抑制剂（sorafenib, regorafenib， lenvatinib和cabozantinib）相关的强烈不良事件（AE）信号，并将这些信号与多个全球机构的监管药物事实进行比较。方法：对美国食品药品监督管理局（FDA）不良事件报告系统（FAERS） 2007 - 2024年的数据进行分析。每个AE被视为二值变量，采用具有稳健误差估计的逻辑回归来识别强信号（优势比> 2,95%置信区间> 1）。将AE信号与FDA（美国）、欧洲药品管理局（EMA，欧盟）、药品和医疗器械管理局（PMDA，日本）和国家药品监督管理局（NMPA，中国）的药品事实进行比较。结果：在33,801个标识符（137,345条记录）中，发现强声发射信号816个。索拉非尼最多（373例），其次是瑞非尼（207例）、lenvatinib（126例）和卡博赞替尼（110例）。值得注意的不良事件包括咽部出血（索拉非尼）、视网膜动脉闭塞（瑞戈非尼）、颅内动脉瘤（lenvatinib）和情绪波动（卡博桑替尼）。32个信号100%可能出现关键结果，不同药物之间没有重叠。ae在男性和老年人群中更为常见。不同监管机构的AE数据差异显著，FAERS数据与监管机构数据重叠较少。结论：本研究对肝癌中四种TKIs的AE信号进行了全面分析，确定了相关性而非因果关系。研究结果强调了AE谱的显著差异以及临床试验数据与真实世界证据之间的差异。这些结果是假设的产生，强调了个性化治疗、加强监测和干预以及改进全球AE报告的必要性，同时承认自发报告系统的固有局限性。

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来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.