{"title":"MET选择性酪氨酸激酶抑制剂的毒性负担模式:来自真实世界药物警戒的证据。","authors":"Wenjie Li, Wei Wang","doi":"10.1007/s10637-024-01437-z","DOIUrl":null,"url":null,"abstract":"<p><p>MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs. Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition demonstrated a substantial prevalence and significance among the adverse event (AE) categories. Particularly notable were the occurrences of peripheral oedema, nausea, dysphagia, fatigue, and dyspnoea, which emerged as the foremost five reported AEs. The majority of these AEs were observed within the initial months of initiating treatment with MET-selective TKIs and persistently thereafter. Notably, our investigation unveiled a significant correlation between the usage of capmatinib and the incidence of hearing loss and difficulty in swallowing. Diligent monitoring and the implementation of supportive care strategies are essential in managing the toxicities associated with MET-selective TKIs, particularly those related to gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and ototoxicity.</p>","PeriodicalId":14513,"journal":{"name":"Investigational New Drugs","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Toxicity burden patterns of MET-selective tyrosine kinase inhibitors: evidence from real-world pharmacovigilance.\",\"authors\":\"Wenjie Li, Wei Wang\",\"doi\":\"10.1007/s10637-024-01437-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs. Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition demonstrated a substantial prevalence and significance among the adverse event (AE) categories. Particularly notable were the occurrences of peripheral oedema, nausea, dysphagia, fatigue, and dyspnoea, which emerged as the foremost five reported AEs. The majority of these AEs were observed within the initial months of initiating treatment with MET-selective TKIs and persistently thereafter. Notably, our investigation unveiled a significant correlation between the usage of capmatinib and the incidence of hearing loss and difficulty in swallowing. Diligent monitoring and the implementation of supportive care strategies are essential in managing the toxicities associated with MET-selective TKIs, particularly those related to gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and ototoxicity.</p>\",\"PeriodicalId\":14513,\"journal\":{\"name\":\"Investigational New Drugs\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Investigational New Drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10637-024-01437-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Investigational New Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10637-024-01437-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
MET第14外显子跳变和MET扩增被认为是癌症患者的致癌和靶向基因变化。MET 选择性酪氨酸激酶抑制剂(TKIs)在这一特定人群中的治疗效果令人鼓舞。然而,目前仍缺乏对这些药物潜在毒性的全面了解。本药物警戒分析利用美国食品药物管理局不良事件报告系统数据库来评估与 MET 选择性 TKIs 相关的显著不良事件。在各类不良事件(AE)中,胃肠功能紊乱、呼吸系统毒性、肝毒性以及代谢和营养紊乱的发生率较高,且具有重要意义。尤其值得注意的是,外周水肿、恶心、吞咽困难、疲劳和呼吸困难成为报告的最主要的五种不良反应。这些不良反应大多出现在开始使用 MET 选择性 TKIs 治疗的最初几个月内,之后持续出现。值得注意的是,我们的调查揭示了使用卡马替尼与听力损失和吞咽困难发生率之间的显著相关性。在管理与MET选择性TKIs相关的毒性,尤其是与胃肠道功能紊乱、呼吸系统毒性、肝毒性和耳毒性相关的毒性时,必须进行严格监测并实施支持性护理策略。
Toxicity burden patterns of MET-selective tyrosine kinase inhibitors: evidence from real-world pharmacovigilance.
MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs. Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition demonstrated a substantial prevalence and significance among the adverse event (AE) categories. Particularly notable were the occurrences of peripheral oedema, nausea, dysphagia, fatigue, and dyspnoea, which emerged as the foremost five reported AEs. The majority of these AEs were observed within the initial months of initiating treatment with MET-selective TKIs and persistently thereafter. Notably, our investigation unveiled a significant correlation between the usage of capmatinib and the incidence of hearing loss and difficulty in swallowing. Diligent monitoring and the implementation of supportive care strategies are essential in managing the toxicities associated with MET-selective TKIs, particularly those related to gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and ototoxicity.
期刊介绍:
The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.