不同EGFR突变位点晚期非小细胞肺癌的临床特征及对靶向药物治疗反应分析

Comparison of clinical outcome and efficacy of patients with advanced non-small cell lung cancer Harbouring different epidermal growth factor receptor mutations

目的探讨不同表皮生长因子受体(EGFR)突变位点晚期非小细胞肺癌(NSCLC)患者的临床特征及其对靶向药物治疗反应的差异。方法收集上海交通大学医学院附属仁济医院具有EGFR外显子19-Del突变及外显子21-L858R突变且接受靶向药物(EGFR-TKI)治疗的晚期NSCLC患者,以RECIST标准评价疗效,比较其临床特征及疗效差异。应用Kaplan-Meier法进行生存分析,比较其肿瘤无进展生存分布是否相同。应用单因素及多因素Cox回归分析探索疾病进展的危险因素。结果 42例入组患者中EGFR外显子19-Del突变者24例,EGFR外显子21-L858R突变者18例。两组患者中除脑转移者比例有显著差异(39%vs.4%,χ~2=8.042,P=0.005)外,其余临床及病理特征均无显著差异。两组患者对EGFR-TKI的总体疗效无显著差异(χ~2=0.803,P=0.669)。EGFR外显子19-Del突变者的中位无进展生存期(PFS)长于EGFR外显子21-L858R突变者(16个月vs.9个月,log-rank P=0.030)。单因素Cox回归分析显示EGFR外显子19-Del突变及肿瘤病理类型为腺癌者有较长的PFS预测因素(P=0.039,P=0.007)。然而多因素Cox回归分析显示EGFR外显子19-Del突变并非较长的PFS独立预测因素(P=0.152)。结论含有EGFR外显子19-Del突变晚期的NSCLC较含有EGFR外显子21-L858R突变者对EGFR-TKI的疗效更好。临床检测EGFR突变位点有助于预测疗效,指导制定治疗方案。

Objective To investigate the clinical impact of epidermal growth factor receptor（EGFR） mutation by retrospectively analysising the clinical outcome of patients with advanced non-small cell lung cancer（NSCLC） treated with EGFR-TKI. Methods Patients with advanced NSCLC harbouring EGFR exon 19-Del and EGFR exon 21-L858R mutation who had received EGFR-TKI treatment in Renji hospital, Shanghai Jiao Tong University School of Medicine were enrolled. Objective response was assessed according to the RECIST 1.1 criteria. Baseline characteristics and response to EGFR-TKI according to EGFR genotype were evaluated. Survival times were estimated using the Kaplane-Meier method. The proportional hazard model was used for univariate and multivariate analysis to assess the independent effect of different mutations. Results The study indentified 42 patients harbouring EGFR exon 19-Del mutation （ n =24） and exon 21-L858R mutation （ n =18） who were treated with EGFR-TKI. 39% of patients with EGFR exon 19-Del mutation had brain metastases, whereas 4% of patients with the exon 21-L858R mutation （χ 2=8.042, P =0.005）. No other significant differences in clinical and pathological characteristics were found between those two groups. Neither was the overall response to EGFR-TKI according to EGFR genotype （χ 2=0.803, P =0.669）. Patients with EGFR exon 19-Del mutation had significantly longer median PFS, compared with patients with EGFR exon 21-L858R mutation （16 vs. 9 months, log-rank P =0.030）. In a Univariate Cox regression model, EGFR exon 19-Del mutation and adenocarcinoma were predictives of longer PFS （ P =0.039, P =0.007）. However, in a multivariate Cox regression model, EGFR exon 19-Del mutation was not independently predictive of longer PFS （ P =0.152）. Conclusion Patients with advanced NSCLC harbouring EGFR exon 19-Del mutation was predictive of higher response and longer median PFS following EGFR-TKI treatment. Thus, screening of patients with advanced NSCLC for EGFR mutations is feasible and can have a vital role in decisions about treatment.