Practical Role of Mutation Analysis for Imatinib Treatment in Patients With Advanced Gastrointestinal Stromal Tumors: A Meta-Analysis

BackgroundImatinib has become the standard first line treatment of gastrointestinal stromal tumors (GIST) in the advanced phase and adjuvant setting. We carried out an up-to-date meta-analysis to determine the practical role of mutation analysis for imatinib treatment in patients with advanced GIST. MethodsEligible studies were limited to imatinib treatment for patients with advanced GIST and reported on mutation analysis. Statistical analyses were conducted to calculate the odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) using fixed-effects and random-effects models. ResultsA total of 2834 patients from 3 randomized controlled trials and 12 cohort studies were included. The ORs of response rates in KIT exon 11-mutant GISTs were 3.504 (95% CI 2.549-4.816, pp=0.001) compared with KIT exon 9-mutant and wild type GISTs, respectively. The HRs of progression-free survival in KIT exon 11-mutant GISTs were 0.365 (95% CI 0.301-0.444, pppp ConclusionPatients with advanced GIST harboring a KIT exon 11 mutation have the best response rate and long-term survival with imatinib treatment. Mutation analysis would be more helpful than KIT expression analysis to decide appropriate therapy for a specific patient.背景 伊马替尼（Imatinib）现已成为晚期及辅助治疗阶段胃肠道间质瘤（gastrointestinal stromal tumors, GIST）的标准一线治疗方案。本研究开展了一项最新的荟萃分析，旨在明确突变检测在晚期GIST患者伊马替尼治疗中的临床应用价值。 方法 本研究纳入的合格研究限定为针对晚期GIST患者采用伊马替尼治疗且报道了突变检测结果的研究。采用固定效应模型与随机效应模型，计算比值比（odds ratio, OR）、风险比（hazard ratio, HR）及95%置信区间（confidence interval, CI）。 结果 本研究共纳入3项随机对照试验与12项队列研究，共计2834例患者。相较于KIT外显子9突变型及野生型GIST，携带KIT外显子11突变的GIST患者的客观缓解率比值比为3.504（95% CI 2.549-4.816，p=0.001）。携带KIT外显子11突变的GIST患者的无进展生存期风险比为0.365（95% CI 0.301-0.444，p<0.001）。 结论 携带KIT外显子11突变的晚期GIST患者接受伊马替尼治疗可获得最优的客观缓解率与长期生存获益。相较于KIT蛋白表达检测，突变检测更有助于为特定患者制定个体化治疗方案。