Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status
Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status
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DOI：
10.1016/j.lungcan.2009.09.010
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发表时间：
2010-07-01
期刊：
影响因子：
5.3
通讯作者：
Voutsina, Alexandra
中科院分区：
文献类型：
--
作者：
Kalikaki, Aristea;Koutsopoulos, Anastasios;Voutsina, Alexandra
背景：EGFR和K-MS的体细胞突变可能预示着对EGFR酪氨酸激酶抑制剂(TKIs)的敏感性和耐药性。研究对象与方法：对162例接受一线化疗的局部晚期/转移性非小细胞肺癌患者进行回顾性研究，根据肿瘤的EGFR和K-ras突变情况分析其临床预后。结果：典型的活化EGFR和K-MS突变分别出现在8.2%和22.6%的非小细胞肺癌患者中，且与患者的临床病理特征无关。与野生型表皮生长因子受体突变的患者相比，具有经典表皮生长因子受体突变的患者对一线化疗的有效率更高(p=0.023)。多因素分析显示，活化的表皮生长因子受体基因突变是影响一线化疗疗效的独立因素(HR=4.85；95%CI：1.13~20.83，P=0.034)。K-RAS突变状态与一线化疗疗效无关。与接受以铂为基础的一线化疗的非小细胞肺癌患者相比，存在激活的表皮生长因子受体而不存在K-RAS突变的患者的总生存率显著增加(p=0.043)。结论：数据表明表皮生长因子受体突变状态可以预测非小细胞肺癌患者对细胞毒一线化疗的反应。还需要更多的前瞻性研究来验证这一观察结果，并确定这些患者是否应该优先接受一线TKI或化疗。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。
Background: Somatic mutations in EGFR and K-MS may predict for sensitivity and resistance to EGFR tyrosine kinase inhibitors (TKIs). Whether EGFR and K-MS mutations could also predict clinical outcome of non-small cell lung cancer (NSCLC) patients following front-line chemotherapy has not yet been established.Patients and methods: One hundred and sixty-two chemotherapy-nave patients with locally advanced/metastatic NSCLC who received front-line chemotherapy were included in this retrospective study and their clinical outcome data was analyzed according to EGFR and K-RAS mutation status of their tumors.Results: Classical activating EGFR and K-MS mutations were found in 8.2 and 22.6% of patients respectively and were not associated with patients' clinicopathological characteristics. Patients with classical EGFR mutations had a higher probability of response to front-line chemotherapy as compared to those with wild type EGFR(p = 0.023). Multivariate analysis showed that the presence of activating EGFR mutations was an independent factor associated with response to front-line chemotherapy (HR = 4.85; 95% CI: 1.13-20.83, p = 0.034). K-RAS mutation status was not associated with response to front-line chemotherapy. The presence of activating EGFR but not of K-RAS mutations was associated with a significantly higher overall survival compared to patients without mutations treated with platinum-based front-line chemotherapy (p = 0.043).Conclusions: The data indicate that EGFR mutation status could be predictive for response to cytotoxic front-line chemotherapy in patients with NSCLC. Additional prospective studies are needed in order to validate this observation and to define whether these patients should be preferentially treated with front-line TKIs or chemotherapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.