摘要
目的非小细胞肺癌(non-small cell lung cancer,NSCLC)中间充质上皮转化因子(mesenchymal epithelial transition factor,MET)异常主要包括MET基因第14号外显子(MET exon 14)跳跃突变(简称METex14跳突)、MET基因扩增及MET蛋白过表达等。METex14跳突是NSCLC的原发致癌驱动变异,在NSCLC患者中的发生率约为0.9%~4%,目前国内外已有多个针对METex14跳突的靶向药物获批上市。NSCLC中原发MET基因扩增发生率约为1%~5%,与不良预后相关。MET基因扩增更常继发于其他驱动基因阳性NSCLC患者靶向治疗后,是表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)耐药的重要机制之一。本调研旨在了解国内MET异常NSCLC患者的诊疗现状、受访医师对MET抑制剂的认知、对于MET异常NSCLC患者治疗决策的考量,同时探求临床实践中未被满足的需求。方法限定时间内诊治过MET异常的医师通过在线问卷形式参与调研,并对结果进行汇总和描述性分析。结果调研共回收140份有效问卷。对于METex14跳突NSCLC,无论初治还是经治,超过50%的受访医师首选MET-TKI单药治疗。≥3级不良事件发生率是最为关注的安全性指标,最关注的不良反应有肺炎、肝毒性和胃肠道不良反应等,对于MET-TKI导致的外周水肿关注度不高。对于EGFR-TKI耐药后MET扩增NSCLC,受访医师首选MET-TKI和EGFR-TKI双靶联合的治疗方案。大型随机对照研究更充分证据、检测有待规范和临床共识是EGFR-TKI耐药后MET扩增NSCLC主要的未被满足的需求。结论MET-TKI在METex14跳突NSCLC的首选比例仍有待提升,对于METTKI导致的外周水肿的关注度需提高以帮助更科学地进行管理。针对不同类型的MET变异的检测还需进一步标准化和规范化。
Objective Mesenchymal epithelial transition(MET)factor alteration in non-small cell lung cancer(NSCLC)mainly includes MET exon 14 skipping alteration(METex14 skipping),MET gene amplification,and MET protein overexpression,etc.METex14 skipping is a driver gene mutation in advanced NSCLC,and the incidence of METex14 skipping in NSCLC patients was 0.9%~4%.Currently,several drugs targeting METex14 skipping have been approved in China and other countries.The incidence of de novo MET gene amplification in NSCLC patients was 1%~5%,which was associated with poor prognosis.MET gene amplification is more frequently occurring after targeted therapy in NSCLC patients with other positive driver genes and is one of the important mechanisms of EGFR-TKI resistance.The purpose of this study is to understand the status of diagnosis and treatment of NSCLC patients with MET alterations in China,including awareness of physicians on MET inhibitors,considerations for treatment decisions of NSCLC patients with MET alterations,and to explore the unmet needs in clinical practice.Method Physicians who had treated MET alteration patients within a defined period participated in the survey through the online questionnaire,and the results were summarized and descriptively analyzed.Results A total of 140 valid questionnaires were collected.For METex14 skipping NSCLC,MET-TKI monotherapy was preferred by more than 50%of the physicians interviewed,regardless of whether patients were treatment naïve or pretreated.The incidence of grade≥3 adverse events(AE)was the most concerned safety indicator,and the most concerned AEs included pneumonia,hepatotoxicity,and gastrointestinal AEs,etc.Peripheral edema caused by MET-TKI was of low concern.For MET-amplified EGFR mutant(EGFRm)NSCLC after EGFR-TKI resistance,the interviewed physicians preferred MET-TKI and EGFR-TKI dual-targeted combination therapy.More sufficient evidence from large-scale randomized controlled studies,standardized testing,and clinical consensus were the major unmet needs for MET-amplified EGFRm NSCLC after EGFR-TKI resistance.Conclusions The preferred proportion of MET-TKI therapy in METex14 skipping NSCLC remains to be improved,and more attention should be paid to MET-TKI-induced peripheral edema to help better management.Testing for different types of MET alteration requires further standardization and normalization.
作者
甘彬
刘思阳
严红虹
吴一龙
GAN Bin;LIU Si-yang;YAN Hong-hong;WU Yi-long(Guangdong Lung Cancer Institute,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China;Department of Hematology,The First Affiliated Hospital,Jinan University,Guangzhou 510630,China)
出处
《循证医学》
2024年第2期97-106,共10页
The Journal of Evidence-Based Medicine
基金
CTONG-默沙东联合基金(CTONG-YC20210201)
中国博士后科学基金第70批面上资助项目(2021M701422)。
作者简介
甘彬(1980-),女,广西南宁人,助理研究员,主要研究方向为临床试验项目实施及管理,研究护士培养及管理;通讯作者:吴一龙,E-mail:syylwu@live.cn。
