EGFR双突变非小细胞肺癌患者临床特征分析

Clinical Features of EGFR Double Mutation in Non-small Cell Lung Cancer

背景与目的非小细胞肺癌(non-small cell lung cancer,NSCLC)中表皮生长因子受体(epidermal growth factor receptor,EGFR)常见单突变患者临床特征研究已经得到广泛认可,女性、无或少吸烟史、腺癌患者中发生率高,经EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)治疗后客观缓解率(objective response rate,ORR)和无进展生存期(progression-free survival,PFS)显著延长。但针对EGFR双突变患者的临床特征以及对EGFR-TKIs治疗的敏感性研究尚不明确。本研究探讨了EGFR双突变患者的临床特征及EGFR-TKIs治疗的疗效。方法收集2015年1月1日-2016年12月31日就诊于青岛大学附属医院接受EGFR基因检测的1,238例原发性NSCLC患者,存在单一突变患者603例,双突变患者59例。所有基因均统一采用ARMS-PCR技术检测。对已明确具体基因分型的32例双突变患者进行基因分析,并随机选取60例单突变患者与59例双突变患者临床特征进行对照,同时比较晚期EGFR双突变和单突变患者对EGFR-TKIs治疗的疗效。结果 EGFR双突变患者中以合并罕见单突变基因最为常见(30/32)。双突变与单突变患者在性别、吸烟史、年龄、病理类型、肿瘤-淋巴结-转移(tumor-node-metastasis,TNM)分期等方面无显著性差异。在接受EGFR-TKIs治疗的双突变患者中,ORR为36.80%,疾病控制率(disease control rate,DCR)为68.40%,中位PFS为6.0个月,单突变患者中ORR为60.00%,DCR为90.00%,中位PFS为12.0个月,两组PFS比较有显著性差异(P=0.003)。结论 EGFR双突变患者的临床特征与单突变患者之间无显著性差异,双突变患者接受一代EGFR-TKIs治疗的ORR、DCR、PFS均较单突变患者低。

Background and objective The clinical features of patients with common single-mutation of epidermal growth factor receptor（EGFR） in non-small cell lung cancer（NSCLC） has been well characterized. There is a high adenocarcinoma incidence rate among female patients with none or shorter smoking history. Those patients have higher objective response rate（ORR） and progression free survival（PFS） treated with EGFR tyrosine kinase inhibitors（EGFR-TKIs）. However, it is still unclear that the clinical features of patients with EGFR double mutation and the sensitivity towards EGFR-TKIs treatment. Methods We performed a retrospective cohort study of 1,238 primary NSCLC patients who had EGFR gene testing in Affiliated Hospital of Qingdao University from January 1, 2015 to December 31, 2016 and identified 603 patients with single mutation and 59 patients with double mutation. All genes were uniformly detected by using ARMS-PCR technology. We analyze the gene of 32 double-mutant patients with specific genotyping, and randomly selected 60 patients with single mutation and compared the clinical features with 59 patients with double mutation. Furthermore, we examined the efficacy of EGFR-TKIs treatment in lung cancer patients with double mutation and single mutation in EGFR. Results The rare single mutation gene is the most common in patients with double mutation of EGFR. There is no significant statistical difference in gender, smoking history, age, pathological type or tumor-node-metastasis（TNM） staging among patients with single and double EGFR mutantion. In the double mutation patients treated with EGFR-TKIs, the objective response rate was 36.80%, the disease control rate was 68.40%. The objective response rate was 60.00% and the disease control rate was 90.00% in the patients with single mutation. However, overall PFS was significantly higher in EGFR single mutation patients（P=0.003）, with median PFS of 12.0 months compared with 6.0 months in EGFR double mutation patients. Conclusion There was no significant difference between the clinical features of patients with EGFR double mutation and single mutation. Patients withEGFR double mutation is associated with poor survival underwent the first generation of EGFR-TKIs treatment compared with patients with a single mutation.