EGFR非第18-21四个外显子突变晚期非小细胞肺癌对不同治疗的反应

The Response of EGFR Non-Exons-18-21-Mutated Advanced Non-Small Cell Lung Cancer to Different Treatments

目的分析表皮生长因子受体(epidermal growth factor receptor,EGFR)非第18-21四个外显子(exons-18-21,Ex18-21)突变晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者对靶向治疗、免疫治疗、化疗的疗效。方法回顾性收集2016-2020年广东省肺癌研究所二代测序(next generation sequencing,NGS)数据库NGS检测出EGFR非Ex18-21单突变肺癌患者35例,EGFR非Ex18-21复合突变肺癌患者65例,2016-2019年广东省肺癌研究所检测出EGFR Ex18-21突变肺癌患者567例。同时收集3组患者的临床病理及治疗数据,分析3组患者的临床病理特征及EGFR非Ex18-21突变肺癌对不同药物的治疗疗效。结果EGFR非Ex18-21复合突变组患者与EGFR Ex18-21组患者在年龄、性别、吸烟史、病理类型、TNM分期上均无统计学差异,而与EGFR非Ex18-21单突变组患者在性别(P<0.001)、吸烟史(P<0.001)、病理类型(P<0.001)分布上有显著差异。EGFR非Ex18-21复合突变组中接受第一代或第二代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)患者(n=26)的中位无进展生存期(progression-free survival,PFS)为9.4个月,在倾向性评分匹配(propensity score matching,PSM)前后,都与EGFR Ex18-21组的中位PFS无显著差异(PSM前:P=0.76;PSM后:P=0.76)。接受第三代EGFR-TKI(n=23)患者的中位PFS为9.5个月,在PSM前后,都与EGFR Ex18-21组的中位PFS无显著差异(PSM前:P=0.23;PSM后:P=0.19)。EGFR非Ex18-21单突变组中,接受免疫治疗患者的中位PFS为4.2个月,接受化疗患者的中位PFS为5.4个月。结论在NGS检出突变后,EGFR非Ex18-21复合突变患者仍能从EGFR-TKI治疗中获益,EGFR非Ex18-21单突变患者接受免疫治疗和化疗的疗效与EGFR野生型患者的疗效相似,未来需要探索EGFR-TKI在EGFR非Ex18-21突变晚期NSCLC患者中的疗效。

Objective To analyze the response of epidermal growth factor receptor(EGFR)non-exons-18-21-mutated advanced non-small cell lung cancer(NSCLC)to targeted therapy,immunotherapy,and chemotherapy.Methods This study collected the clinical data of 35 patients with EGFR non-exons-18-21 pure mutation and 65 patients with EGFR nonexons-18-21 compound mutation in the next generation sequencing(NGS)database of Guangdong Lung Cancer Institute(GLCI)from 2016 to 2020,and collected the clinical data of 567 patients with EGFR exons-18-21 mutation in GLCI from2016 to 2019.Clinicopathological characteristics of the three groups were compared,and the response of patients withEGFR non-exons-18-21 mutations to different treatments were analyzed.Results The clinicopathological characteristics of the EGFR non-exons-18-21 compound mutation group were consistent with those of the EGFR exons-18-21 mutation group,but showed significant differences in gender(P<0.001),smoking history(P<0.001),and pathological type(P<0.001)compared with those of the EGFR non-exons-18-21 pure mutation group.In the EGFR non-exons-18-21 compound mutation group,the progression-free survival(PFS)of patients receiving first-or second-generation EGFR-tyrosine kinase inhibitors(TKIs)(n=26)was 9.4 months,which was no significant difference from that of patients with EGFR exons-18-21 mutation with or without propensity score matching(PSM)(before PSM:P=0.76;after PSM:P=0.76).And the PFS of patients receiving third-generation EGFR-TKIs(n=23)was 9.5 months,which was also no significant difference from that of patients with EGFR exons-18-21 mutation with or without PSM(before PSM:P=0.23;after PSM:P=0.19).In EGFR non-exons-18-21pure mutation group,the PFS of patients receiving immunotherapy and chemotherapy were 4.2 months and 5.4 months,respectively.Conclusions After NGS detected EGFR non-exons-18-21 mutation,patients with EGFR non-exons-18-21compound mutations could also benefit from first-to third-generation EGFR-TKIs.And the response of immunotherapy and chemotherapy in patients with EGFR non-exons-18-21 pure mutations were similar to that of EGFR wild-type NSCLC.In the future,we need to explore the efficacy of EGFR-TKIs in EGFR non-exons-18-21 pure mutated NSCLC.