晚期非小细胞肺癌患者的表皮生长因子受体突变

[EGFR mutations in patients with advanced NSCLC].

作者信息

Fiala O, Pešek M, Fínek J, Brůha F, Bortlíček Z, Krejčí J, Benešová L, Minárik M

机构信息

Onkologicke a radioterapeuticke oddeleni, FN Plzen, Plzen-Lochotin.

出版信息

Klin Onkol. 2012;25(4):267-73.

PMID:22920167

Abstract

BACKGROUND

Molecular targeted therapy based on tyrosine kinase inhibitors, directed at the epidermal growth factor receptor (EGFR) is one of novel options for management of NSCLC. EGFR gene mutations, exon 19 deletions and exon 21 point mutations (L858R) are good predictors of response to EGFR-TKI treatment. The aim of this study was to assess the incidence of EGFR mutations in a large cohort of Europeans with advanced NSCLC and subsequently to evaluate their impact on the effect of EGFR-TKI treatment.

PATIENTS AND METHODS

In total, 613 patients with advanced stage NSCLC (IIIB, IV) were genetically tested. The effect of treatment was evaluated in 410 patients treated with EGFR-TKI. Survival was evaluated using Kaplan-Meier method, and statistical comparison was performed using log-rank test.

RESULTS

EGFR mutations were detected in 73 (11.9%) patients. Exon 19 deletions were detected in 49 patients, exon 21 point mutations (L858R) were detected in 22 patients, and both mutation types were detected in 2 patients. An increased incidence of EGFR mutations among patients with adenocarcinoma (14.9% vs 7.8%, p = 0.008), women (20.2% vs 7.1%, p < 0.001) and nonsmokers (29.9% vs 7.0%, p < 0.001) was demonstrated. Sixty patients with EGFR mutation and 350 patients with wild-type EGFR were treated with EGFR-TKI. Median PFS in patients harboring EGFR mutation was 7.2 vs 2.0 months in patients harboring wild-type EGFR (p < 0.001), median OS in patients harboring EGFR mutation was 14.5 vs 7.5 months in patients harboring wild-type EGFR (p = 0.019).

CONCLUSION

The incidence of EGFR mutations in the studied population, their increased incidence among patients with adenocarcinoma, women and non-smokers correlated with data previously published. Results of survival analysis in patients treated with EGFR-TKI confirmed high potential of EGFR mutations to predict good effect of the EGFR-TKI treatment. Genetic testing in patients with NSCLC should be a standard part of diagnostic procedures

摘要

背景

基于酪氨酸激酶抑制剂、针对表皮生长因子受体（EGFR）的分子靶向治疗是晚期非小细胞肺癌（NSCLC）治疗的新选择之一。EGFR基因突变、外显子19缺失和外显子21点突变（L858R）是EGFR-TKI治疗反应的良好预测指标。本研究的目的是评估一大群欧洲晚期NSCLC患者中EGFR突变的发生率，并随后评估其对EGFR-TKI治疗效果的影响。

患者与方法

总共对613例晚期NSCLC（IIIB期、IV期）患者进行了基因检测。对410例接受EGFR-TKI治疗的患者的治疗效果进行了评估。使用Kaplan-Meier方法评估生存率，并使用对数秩检验进行统计学比较。

结果

在73例（11.9%）患者中检测到EGFR突变。49例患者检测到外显子19缺失，22例患者检测到外显子21点突变（L858R），2例患者同时检测到两种突变类型。腺癌患者（14.9%对7.8%，p = 0.008）、女性患者（20.2%对7.1%，p < 0.001）和非吸烟者（29.9%对7.0%，p < 0.001）中EGFR突变的发生率增加。60例EGFR突变患者和350例EGFR野生型患者接受了EGFR-TKI治疗。EGFR突变患者的中位无进展生存期为7.2个月，而EGFR野生型患者为2.0个月（p < 0.001），EGFR突变患者的中位总生存期为14.5个月，而EGFR野生型患者为7.5个月（p = 0.019）。