EGFR-TKI一线治疗EGFR基因突变的晚期非小细胞肺癌临床观察

Clinical Observation of EGFR-TKI as A First-line Therapy on Advanced Non-small Cell Lung Cancer

背景与目的研究表明,一线表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitor,EGFR-TKI)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的客观缓解率及无进展生存期明显优于铂二联的化疗,且耐受性更好。本研究旨在分析EGFR-TKI一线治疗晚期EGFR突变阳性的NSCLC患者的疗效与耐受性。方法 54例晚期NSCLC患者肿瘤标本采用直接测序法证实EGFR活化突变(外显子19缺失或外显子21点突变),一线给予EGFR-TKI口服治疗直至疾病进展,观察疗效及不良反应,并进行生存随访。结果 54例患者外显子19缺失33例(61%),外显子21点突变21例(39%)。均一线接受EGFR-TKI治疗,总体缓解率为90%,中位无进展生存期(progression free survival,PFS)为8.3个月,中位生存期为19.5个月;外显子19缺失患者的中位PFS(9.0个月)较21点突变(7.0个月)时间长(P=0.002)。外显子19缺失患者的中位总生存期(overall survival,OS)(25.0个月)较21点突变(16.0个月)时间长(P=0.001);吉非替尼与厄洛替尼疗效相当,但吉非替尼组安全性更好;最常见的不良事件为皮疹和腹泻,有2例患者(4%)出现了3度皮肤毒性反应,2例患者(4%)出现了3度的转氨酶升高,1例患者(1%)出现了3度口腔炎。结论存在EGFR基因突变的晚期NSCLC患者一线接受EGFR-TKI治疗安全有效,且外显子19缺失比L858R突变疗效更优。

Background and objective It has been proven that epidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI） significantly benefits advanced non-small cell lung cancer（NSCLC） patients harboring EGFR mutations in progression-free survival time with better tolerance.This study is undertaken to analyze efficacy and tolerance of advanced NSCLC patients harboring EGFR mutations taking EGFR-TKI as a first-line therapy.Methods Tumor samples from 54 patients with advanced NSCLC were examined for EGFR activating mutations（deletion mutation in exon 19 and the L858R point mutation in exon 21） by direct sequencing.The patients were first-line treated with oral administration of EGFRTKI until disease progression.The efficacy and adverse events were observed,and survival was followed up.Results Among the patients,61%（33 of 54） had EGFR exon 19 deletion,and 39%（21 of 54） had EGFR L858R point mutation.All patients received first-line TKI therapy.The total response rate was 96%,median progression free survival（PFS） was 8.3 months and median survival was 19.5 months.The patients with EGFR exon 19 deletion had significantly longer median PFS（9 versus 7 months,P=0.002） and longer median overall survival（OS）（25 versus 16 months,P=0.001） than patients with EGFR L858R point mutation.There is no significance in efficacy between gefitinib and erlotinib,and gefitinib is safer than erlotinib.The most common adverse events were rash and diarrhea.Two（4%） grade 4 skin toxity effects,two（4%） grade 3 aminotransferase level elevations,and one（1） grade 3 stomatitis were observed.Conclusion The first-line EGFR-TKI treatment in advanced NSCLC patients harboring EGFR mutations is efficient and safe,which is more efficient in patients with EGFR exon 19 deletion than those with EGFR L858R mutation.