Somatic EGFR Mutation and Gene Copy Gain as Predictive Biomarkers for Response to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer
Somatic EGFR Mutation and Gene Copy Gain as Predictive Biomarkers for Response to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-09-1660
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发表时间：
2010-01-01
影响因子：
11.5
通讯作者：
Murray, Samuel
中科院分区：
文献类型：
--
作者：
Dahabreh, Issa J.;Linardou, Helena;Murray, Samuel
目的：本系统回顾和荟萃分析的目的是描述常见的EGFR分子异常作为预测非小细胞肺癌(NSCLC)对酪氨酸激酶抑制剂(TKI)单一治疗反应的潜在生物标志物。实验设计：我们系统地确定了研究接受TKI治疗的非小细胞肺癌患者的EGFR状态[体细胞突变和基因复制异常(拷贝数)]的文章。符合条件的研究必须报告按EGFR状态分层的完全应答率和部分应答率。结果：在222篇检索到的文献中，59篇符合体细胞EGFR突变Meta分析标准(3101例患者中1,020个突变)，21篇符合EGFR基因拷贝数Meta分析标准(1,539例患者中有542个基因获得)。EGFR突变可预测单药TKIs的疗效[敏感度，0.78；95%可信区间(95%CI)，0.74~0.82；特异度，0.86；95%CI，0.82~0.89；+LR，5.6；-LR，0.25]。EGFR基因的获得也与TKI的反应有关，尽管敏感性和特异性较低。在亚组分析中，唯一公认的趋势是白人的突变和基因拷贝数比东亚人更高的预测值。结论：这一分析提供了经验证据，表明EGFR突变是晚期非小细胞肺癌患者对单剂表皮生长因子受体TKIs反应的敏感和特异的预测因子。突变的诊断性能似乎比EGFR基因获得更好。临床癌症资源；16(1)；291-303。(C)2010年AACR。
Purpose: The aim of this systematic review and meta-analysis was to characterize common EGFR molecular aberrations as potential predictive biomarkers for response to monotherapy with tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC).Experimental Design: We systematically identified articles investigating EGFR status [somatic mutational and gene copy aberrations (copy number)] in patients with NSCLC treated with TKIs. Eligible studies had to report complete and partial response rates stratified by EGFR status. We used random effects models for bivariable meta-analysis of sensitivity and specificity; positive and negative likelihood ratios (+LR and -LR, respectively) were also calculated and were considered as secondary end points.Results: Among 222 retrieved articles, 59 were considered eligible for the somatic EGFR mutation meta-analysis (1,020 mutations among 3,101 patients) and 21 were considered eligible for the EGFR gene copy number meta-analysis (542 gene gain among 1,539 patients). EGFR mutations were predictive of response to single-agent TKIs [sensitivity, 0.78; 95% confidence interval (95% CI), 0.74-0.82; specificity, 0.86; 95% CI, 0.82-0.89; +LR, 5.6; -LR, 0.25]. EGFR gene gain was also associated with response to TKIs, albeit with lower sensitivity and specificity. In subgroup analysis, the only recognized trend was for a higher predictive value in Whites compared with East Asians for both mutation and gene copy number.Conclusion: This analysis provides empirical evidence that EGFR mutations are sensitive and specific predictors of response to single-agent epidermal growth factor receptor TKIs in advanced NSCLC. The diagnostic performance of mutations seems better than that of EGFR gene gain. Clin Cancer Res; 16(1); 291-303. (C)2010 AACR.