KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies
KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies
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DOI：
10.1016/j.lungcan.2009.11.020
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发表时间：
2010-09-01
期刊：
影响因子：
5.3
通讯作者：
Chen, Qing
中科院分区：
文献类型：
--
作者：
Mao, Chen;Qiu, Li-Xin;Chen, Qing
流行病学研究已经评估了KRAS突变与非小细胞肺癌(NSCLC)患者对表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)治疗耐药的相关性。然而，结果并不确定。为了更准确地估计这种关系，我们进行了这项荟萃分析。对PubMed和Medline数据库进行了系统的计算机搜索(截至2009年6月30日)。共有22项研究被纳入最终的荟萃分析，包括1470名非小细胞肺癌患者，其中231人有KRAS突变(16%)。现吸烟者或曾经吸烟者的KRAS突变频率高于从不吸烟者(25%比6%；OR=4.36；P<；0.01)。突变在腺癌中比在其他组织中更常见(26%对16%；OR=1.98；P<；0.01)。突变KRAS患者客观有效率为3%(6/210)，野生型KRAS患者客观有效率为26%(287/1125)。ORR的总体合并RR为0.29(95%CI：0.18-0.47；P<；0.01)。分组分析是在种族和研究处理的基础上进行的，所有结果都没有实质性改变，也没有得出不同的结论，表明我们的结果是稳健的。综上所述，这一荟萃分析表明，KRAS突变可能代表接受EGFR-TKIs治疗的非小细胞肺癌患者肿瘤反应的阴性预测生物标志物。然而，由于KRAS突变与Eger突变之间存在互斥关系，且KRAS突变型/EGFR野生型与KRAS野生型/EGFR野生型NSCLC的生存率无明显差异，KRAS突变作为EGFR-TKIs敏感性的选择标志物在非小细胞肺癌中的临床应用受到限制。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。
Epidemiologic studies have evaluated the association between KRAS mutations and resistance to the treatment of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, results were inconclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic computerized searches of the PubMed and Medline databases (up to Jun 30, 2009) were performed. A total of 22 studies were included in the final meta-analysis, consisting of 1470 NSCLC patients, of whom 231 had KRAS mutations (16%). Current or former smokers had a higher frequency of KRAS mutations than never smokers (25% versus 6%; OR = 4.36; P < 0.01). Mutations were more common among adenocarcinoma than other histologies (26% versus 16%; OR = 1.98; P < 0.01). The objective response rate (ORR) of NSCLC patients with mutant KRAS was 3% (6/210), whereas the ORR of NSCLC patients with wild-type KRAS was 26% (287/1125). The overall pooled RR for ORR was 0.29 (95% CI: 0.18-0.47; P < 0.01). Subgroup analyses were conducted on the basis of ethnicity and study treatment, all the results were not materially altered and did not draw different conclusions, indicating that our results were robust. In summary, this meta-analysis suggests that KRAS mutations may represent negative predictive biomarkers for tumor response in NSCLC patients treated with EGFR-TKIs. However, due to a mutually exclusive relationship between KRAS and EGER mutation and no difference in survival between KRAS mutant/EGFR wild-type and KRAS wild-type/EGFR wild-type NSCLC, the clinical usefulness of KRAS mutation as a selection marker for EGFR-TKIs sensitivity in NSCLC is limited. (C) 2009 Elsevier Ireland Ltd. All rights reserved.