Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib
Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib
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DOI：
10.1200/jco.2005.02.857
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发表时间：
2005-09-01
影响因子：
45.3
通讯作者：
Hillan, KJ
中科院分区：
文献类型：
--
作者：
Eberhard, DA;Johnson, BE;Hillan, KJ
目的 表皮生长因子受体（EGFR）突变与复发非小细胞肺癌（NSCLC）患者对单药EGFR抑制剂治疗的肿瘤反应相关。在接受EGFR抑制剂加一线化疗的患者中，EGFR突变的影响尚不明确。KRAS在NSCLC中经常被激活。KRAS突变与EGFR抑制剂治疗后的结果之间的关系尚未被描述。
患者和方法 在Ⅲ期TRIBUTE研究中，先前未经治疗的晚期NSCLC患者被随机分配接受卡铂和紫杉醇联合厄洛替尼或安慰剂治疗，对其生存、反应和进展时间（TTP）进行评估。对274例患者的肿瘤进行了EGFR外显子18 - 21和KRAS外显子2测序。在回顾性亚组分析中，将结果与EGFR和KRAS突变相关联。
结果 在13%的肿瘤中检测到EGFR突变，且无论治疗如何，其都与更长的生存期相关（P
Purpose Epidermal growth factor receptor (EGFR) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung Cancer (NSCLC). The implications of EGFR mutations in patients treated with EGFR inhibitors, plus first-line chemotherapy are unknown. KRAS is frequently activated in NSCLC. The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described.Patients and Methods Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were randomly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival, response, and time to progression (TTP). EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients. Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses.Results EGFR mutations were detected in 13% of tumors and were associated with longer survival, irrespective of treatment (P