晚期非小细胞肺癌表皮生长因子受体基因突变情况和其对吉非替尼疗效的影响

摘要

背景与目的 研究晚期非小细胞肺癌( non-small cell lung cancer,NSCLC)表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变情况和该基因突变状态对吉非替尼疗效的影响.方法 于2007年1月-2009年12月对160例晚期非鳞癌NSCLC患者进行了EGFR基因检测,EGFR基因外显子19和外显子21突变检测采用突变富集PCR法.其中111例接受了吉非替尼治疗.中位生存期(overall survival,OS)和无疾病进展生存时间(progression free survival,PFS)的比较采用Kaplan-Meier方法计算.结果 晚期非鳞癌NSCLC患者EGFR基因突变率为55％,多因素分析显示只有病理类型与是否突变明显相关.EGFR基因突变型患者的OS为29.0个月(95％CI:24.2-33.8),野生型为21.0个月( 95％CI:14.7-27.3),两者差别无统计学差异.EGFR基因突变患者的PFS为17.0个月(95％CI:5.6-17.6),而野生型为11.6个月(95％CI:8.6-25.4),两者有明显性差别(P=0.022).OS的多因素分析结果显示,OS与ECOG评分、病理类型、EGFR基因突变状态明显相关.PFS多因素分析结果显示,PFS与ECOG评分、既往化疗方案数和EGFR基因突变明显相关.EGFR基因外显子19突变与外显子21突变的OS和PFS无明显差别,客观疗效也无差别.结论 晚期非鳞癌NSCLC EGFR基因突变患者的PFS明显优于野生型患者,OS有延长趋势.EGFR基因不同突变类型的PFS和OS均无差别.%Background and objective It has been proven that the status of epidermal growth factor receptor (EGFR) gene mutation was related to effects of gefitinib in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study is to reports distribution of EGFR gene mutations in advanced NSCLC and their influence on effect of gefitinib. Methods From Jan 2007 to Dec 2009, 160 patients with advanced non-squamous NSCLC received EGFR mutation tests, and EGFR exon 19 and 21 were amplified by mutant-enriched PCR and analyzed by sequencing. Among those patients, 111 received gefitinib therapy. Overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan-Meier method and a Cox regression analysis was used to detect differences between strata. Results The percentage of EGFR mutation in advanced non-squamous NSCLC was 55%, and it was only significantly related with pathological type. OS of the patients with or without EGFR gene mutations were 29.0 months (95%CI: 24.2-33.8) and 21.0 months (95%CI: 14.7-27.3) respectively, and the difference was not significant. PFS of patients with or without EGFR gene mutations were 17.0 months (95%CI: 5.6-17.6) and 11.6 months (95% CI 8.6-25.4), and the difference was significant (P=0.022). Multi-variate analysis shows that OS was significantly related with ECOG status, pathological type and EGFR mutation statuses, and PFS was significantly related to ECOG status, former regimens number and EGFR mutation statuses. There were no significant differences in OS and PFS between patients with EGFR exon 19 deletions and those with exon 21 point mutation. Conclusion PFS of patients with EGFR mutations was better than those without EGFR mutations, but OS was similar. There were no significant differences in OS and PFS between patients with EGFR exon 19 deletions and those with exon 21 point mutation.