Investigation of therapeutic modalities of G719X, an uncommon mutation in the EGFR gene in non-small cell lung cancer

Objective G719 X is the most frequently seen uncommon mutation of the epidermal growth factor receptor(EGFR) gene, which is a point mutation at exon 18 with three common subtypes, G719 A/G719 C/G719 S. This study explored the clinicopathological characteristics of the G719 X mutation and investigated the efficacy of EGFR-tyrosine kinase inhibitor(TKI) treatment and chemotherapy in patients with the G719 X mutation; the survival rate after these different treatment modalities were then analyzed in order to provide evidence for clinical treatment.Methods Clinical data of 41 patients with the G719 X mutation admitted in the Beijing Chest Hospital, Capital Medical University from September 2014 to July 2018, were collected and the EGFR mutations were detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR). The clinicopathological characteristics of the G719 X mutation were analyzed, and the relationship among the G719 X mutation, the efficacy of different treatment modalities, and the progression-free survival(PFS) was analyzed. Results Of the 41 cases, 24(58.5%) were G719 X single mutations and 17(41.5%) were compound mutations, including G719 X/S768 I, G719 X/L861 Q, G719 X/19 del, and G719 X/c-Met compound mutation. The objective response rate(ORR) of first-line EGFR-TKI therapy was 50%(6/12), the disease control rate(DCR) was 83.3%(10/12), and the median PFS(mPFS) was 9 months. After resistance to EGFR-TKI in the previous treatment, the ORR(71.4%, 5/7) and DCR(100%, 7/7) were still high following EGFR-TKIs, by an mPFS of 8 months. The ORR of chemotherapy was 33.3%(2/6), the DCR was 100%(6/6), and the mPFS was 6 months. Conclusion G719 X is an uncommon mutation of the EGFR gene and is sensitive to many EGFR-TKIs. It can be treated with the second-or third-generation EGFR-TKIs after resistance to the first-generation EGFR-TKIs. G719 X mutation also showed favorable effect to chemotherapy.

5例非小细胞肺癌G719X突变临床特征及治疗疗效

目的:探讨5例非小细胞肺癌G719X突变临床特征、治疗方法及疗效评估。方法:纳入2012年07月至2018年12月在空军军医大学第二附属医院呼吸与危重症医学科基因检测中心行EGFR基因检测的705例非小细胞肺癌患者,回顾性分析其G719X突变临床特征及疗效。结果:705例非小细胞肺癌患者中G719X复合突变4例,单一突变1例,G719X突变者均是Ⅳ期腺癌,无糖尿病、无高血压且未并发其它肿瘤,组织突变率低于血液、积液突变率,女性突变率高于男性,小于50岁组突变率高于大于等于50岁组,不吸烟组突变率高于吸烟组,合并骨转移、脑转移、淋巴结转移、胸膜转移组突变率分别高于无转移组,右肺肿瘤突变率略高于左肺肿瘤,但以上差异均无统计学意义;3例突变一线接受一代EGFR-TKI治疗,OS最长22月,为G719X+S768I复合突变者。结论:G719X突变以G719X+L861Q复合突变为主,Ⅳ期腺癌,无糖尿病、无高血压且未并发其它肿瘤者更易出现。在标本类型、年龄、性别、是否吸烟、病变部位、是否并发骨、脑、淋巴结、胸膜转移方面突变率比较差异均无统计学意义;一线接受一代EGFR-TKI治疗或化疗患者生存可获益。