瑞派替尼加量治疗晚期胃肠道间质瘤临床效果的全国多中心研究  

Clinical efficacy of ripretinib dose escalation for the treatment of advanced gastrointestinal stromal tumors:a nationwide and multicenter study

作　　者：张信华[1] 孙小峰[2] 张业繁[3] 毛凯[4] 刘洪俊[5] 刘宁 周烨[7] 蒙燕 檀碧波[9] 王烈 齐长松 康荣彬 周永建[12] Zhang Xinhua;Sun Xiaofeng;Zhang Yefan;Mao Kai;Liu Hongjun;Liu Ning;Zhou Ye;Meng Yan;Tan Bibo;Wang Lie;Qi Changsong;Kang Rongbin;Zhou Yongjian(Center of Gastrointestinal Surgery,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Department of Oncology,Jiangsu Cancer Hospital,Nanjing 210009,China;Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences,Beijing 100021,China;Department of Hepatobiliary Pancreatic Surgery,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Department of Gastrointestinal Surgery,Shandong Provincial Hospital,Jinan 250021,China;Department of Gastric Surgery,Tianjin Medical University Cancer Institute&Hospital,Tianjin 300060,China;Department of Gastric Surgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China;Department of Oncology,Hainan Cancer Hospital,Haikou 570312,China;The Third Department of General Surgery,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Department of General Surgery,the 900th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army,Fuzhou 350399,China;Department of Gastroenterology and Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Gastric Surgery,Fujian Medical University Union Hospital,Fuzhou 350001,China)

机构地区：[1]中山大学附属第一医院胃肠外科中心,广州510080 [2]江苏省肿瘤医院肿瘤内科,南京210009 [3]中国医学科学院肿瘤医院肝胆外科,北京100021 [4]中山大学孙逸仙纪念医院肝胆胰外科,广州510120 [5]山东省立医院胃肠外科,济南250021 [6]天津医科大学肿瘤医院胃部肿瘤科,天津300060 [7]复旦大学附属肿瘤医院胃外科,上海200032 [8]海南省肿瘤医院肿瘤内科,海口570312 [9]河北医科大学第四医院外三科,石家庄050011 [10]中国人解放军联勤保障部队第九○○医院普通外科,福州350399 [11]北京大学肿瘤医院消化肿瘤内科,北京100142 [12]福建医科大学附属协和医院胃外科,福州350001

出　　处：《中华消化外科杂志》2024年第3期392-397,共6页Chinese Journal of Digestive Surgery

基　　金：白求恩·肿瘤基础研究计划(BCF‑NH‑ZL‑20201119‑001)。

摘　　要：目的探讨瑞派替尼加量治疗晚期胃肠道间质瘤(GIST)的临床效果。方法采用回顾性描述性研究方法。收集2020年1月至2022年10月中山大学附属第一医院等全国12家医学中心收治的14例晚期GIST患者的临床病理资料;男9例,女5例;年龄为63(40~73)岁。患者均行瑞派替尼加量治疗。观察指标:(1)患者临床特征情况。(2)瑞派替尼治疗效果。偏态分布的计量资料以M(范围)表示。计数资料以绝对数表示。采用Kaplan‑Meier法绘制生存曲线并计算生存时间。结果(1)患者临床特征情况。14例患者中,肿瘤原发部位在小肠、胃、其他分别为8、4、2例,肿瘤转移部位在肝脏、腹膜、骨、肺分别为13、9、4、2例(每例患者可发生>1种转移),转移肿瘤数目1~5个、6~10个、>10个分别为2、8、4例,有手术史或转移灶局部消融治疗11例,既往治疗线数≤2线、≥3线分别为3、11例,既往治疗药物采用伊马替尼、舒尼替尼、瑞戈非尼、阿伐替尼分别为14、13、9、2例(每例患者治疗药物可>1种)。14例患者均进行基因检测,KIT外显子11合并外显子13基因突变5例,KIT外显子11合并外显子17基因突变4例,KIT外显子11合并外显子13和17基因突变2例,KIT外显子9合并外显子17基因突变、KIT外显子11突变和野生型各1例;其中继发基因突变12例。(2)瑞派替尼治疗效果。14例患者均获得随访,随访时间为17.3(4.4~30.0)个月。①瑞派替尼标准四线治疗:14例患者均行瑞派替尼标准四线治疗,治疗持续时间为6.0(2.0~17.0)个月,完全缓解、部分缓解、疾病稳定分别为1、2、11例,客观缓解占比为3/14,疾病控制占比为14/14;中位无进展生存时间为6.0个月。14例患者中,11例发生1~2级不良事件,均未发生3~4级不良事件。②瑞派替尼加量治疗:14例患者行瑞派替尼标准四线治疗后均发生疾病进展,均行瑞派替尼加量治疗,其中12例行150 mg 2次/d治疗,2例行200 mg 1次/d治疗�Objective To investigate the clinical efficacy of ripretinib dose escalation for the treatment of advanced gastrointestinal stromal tumors(GIST).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 14 patients with advanced GIST who were admitted to 12 medical centers,including The First Affiliated Hospital of Sun Yat-sen University et al,from January 2020 to October 2022 were collected.There were 9 males and 5 females,aged 63(range,40−73)years.All patients underwent ripretinib dose escalation treatment.Observation indicators:(1)clinical characteristics of patients;(2)clinical efficacy of ripretinib treatment.Measurement data with skewed distribution were represented as M(range),and count data were described as absolute numbers.The Kaplan-Meier method was used to draw survival curve and calculate survival time.Results(1)Clinical characteristics of patients.Of the 14 patients,cases with primary tumor located at small intestine,stomach and others were 8,4,2,respectively,and cases with tumor metastasis to liver,peritoneum,bone and lung were 13,9,4,2,respectively(one patient may experience more than one type of metastasis).Cases with number of metastatic tumor as 1−5,6−10 and>10 were 2,8,4,respectively.There were 11 patients with a history of surgery or local ablation treatment for metastatic lesions.Cases with previous treatment lines as≤2 and≥3 were 3 and 11,respectively.Cases with previous treatment drugs as imatinib,sunitinib,regofinib and atorvatinib were 14,13,9 and 2,respectively(one patient may have more than one type of medication).All 14 patients underwent genetic testing,including 5 cases of KIT exon 11 combined with exon 13 gene mutation,4 cases of KIT exon 11 combined with exon 17 gene mutation,2 cases of KIT exon 11 combined with exon 13 and 17 gene mutation,1 case of KIT exon 9 combined with exon 17 gene mutation,1 case of KIT exon 11 mutation and 1 case of wild-type gene type.There were 12 cases with secondary gene mutations.(2)Clinical efficacy of ri

关 键 词：胃肠道间质瘤 瑞派替尼 加量治疗 疗效 安全性 

分 类 号：R735[医药卫生—肿瘤]