突变型EGFR表达量与TKI治疗晚期肺腺癌疗效的相关性分析

目的探讨易瑞沙单药治疗晚期非小细胞肺癌患者的疗效与EGFR突变状况、mRNA表达量及不良反应的关系。方法 2007年1月至2008年10月共52例符合腺癌、不吸烟的晚期非小细胞肺癌患者接受易瑞沙250mg/d口服治疗,检测EGFR突变状况、观察患者的疗效、TTP、MST和毒副反应。结果本组52例患者均可评价疗效,其中完全缓解3例,部分缓解21例,无变化22例,进展6例。有效率为46.2%,疾病控制率为88.5%,中位TTP为454.67d,1年无进展生存率为52%,MST为597.9d,1年生存率为60%。47例有效检测病例中EGFR突变30例,突变率63.82%。其中高丰度组19例,低丰度组11例。EGFR高丰组患者中TKI治疗有效(CR+PR)的16例,统计结果表明:EGFR突变组EGFR-TKI治疗有效率、疾病控制率显著高于无突变组(P<0.05)。扩增高丰度组有效率、疾病控制率比低丰组无扩增病例组显著增高(P<0.05),提示EGFR基因表达量与疗效有显著相关性。不良反应主要为皮疹和腹泻。有效率与患者性别、年龄、一般状况、分期及既往治疗无关,与皮疹相关(ORR=0.143,95%CI:0.035-0.590)。TTP与患者性别、一般状况、分期及既往治疗无关,患者年龄、腹泻与TTP相关。50岁以下无腹泻的患者疾病进展风险增加(HR=4.196,P=0.0005)。结论易瑞沙治疗河南本地腺癌、不吸烟的晚期NSCLC的疗效显著,总体生存明显获益,不良反应轻微。EGFR突变及mRNA表达量是评价疗效的重要因素。

A nalysis of multi-factors in Tyrosine kinase antagonist treatment of advanced non-small cell lung cancer

Objective To investigate the efficacy and toxicity of Iressa in treatment of clinically selected patients with advanced non-small cell lung cancer(NSCLC) and EGFR mutation status,adverse reactions.Methods From Jan 2007 to Oct 2008,52 advanced NSCLC patients(non-smokers,adenocarcinoma,from Henan Province) were retrospectively reviewed.All patients had received Iressa 250mg/d of oral.Then detected the EGFR mutation status,observed the treatment effect,TTP,MST and toxicity.Results All 52 patients could be evaluated,including complete remission in 3 cases and partial remission in 21 cases,unchanged in 22 cases,progress in 6 cases.Effective rate was 46.2%,disease control rate was 88.5%,median TTP was 454.67 days,1-year progression-free survival rate was 52%,MST of 597.9 days,1 year survival rate was 60%.In the 47 effective detection cases,there was 30 cases of EGFR mutations,mutation rate was 64%.Including 19 cases with high abundance group,11 patients with low abundance.In the high abundance of EGFR mutation,16 canses is effective(CR+PR) to TKI treatment.TKI therapy efficiency,disease control rate in EGFR mutation group was significantly higher than non-mutation group(P<0.05).Constrasts to patients with non-amplification of low abundance,the efficacy and disease control rate in patients with amplification of high-abundance group was significantly higher(P<0.05),suggest that there was significant association between EGFR gene expression and efficacy.The common adverse reactions were rash and diarrhea.There was no statistically significant association between efficacy and patient gender,age,general condition,stage or previous treatment,but there was relationship between efficacy and rash.(ORR=0.143,95% CI:0.035～0.590).There was significant association between TTP and patient age,diarrhea,no statistically significant association between TTP and sex,general condition or stage.Less than50 years of age without diarrhea in patients at increased risk of disease progression(HR=4.196,P=0.0005).Conclusions Iressa is effective in treatment of advanced NSCLC patients(non-smokers,adenocarcinoma,from Henan Province),OS is significantly prolonged and the adverse effects are tolerable.EGFR mutations and mRNA expression is an important factor to evaluate efficacy.