肺鳞癌患者EGFR基因突变状态与EGFR-TKIs疗效分析
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摘要
[目的]分析肺鳞癌患者表皮生长因子受体(EGFR)基因的突变状态,观察表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)对EGFR敏感突变肺鳞癌患者的临床疗效。[方法]回顾性分析广西医科大学附属肿瘤医院2013年11月至2017年8月行EGFR基因检测的肺鳞癌患者172例,利用突变扩增阻滞系统(ARMS)的方法进行EGFR基因检测,分析患者的临床病理特征,随访EGFR-TKIs靶向治疗的EGFR敏感突变肺鳞癌患者。[结果] 172例肺鳞癌患者中,EGFR基因敏感突变15例,突变率为8.7%,在EGFR基因突变患者中,女性、不吸烟患者EGFR基因突变率高于男性、吸烟患者(22.2%vs 5.1%,16.7%vs4.5%)(P=0.001,P=0.007)。不同分化程度、不同分期、标本类型、癌胚抗原、鳞状细胞癌相关抗原正常或升高之间EGFR基因突变率差异无统计学意义(P>0.05)。EGFR基因敏感突变肺鳞癌患者中,5例一线、1例二线使用EGFR-TKIs治疗,其客观有效率为33.3%,疾病控制率为83.3%,中位无进展生存期为4.9个月,中位总生存期为10.75个月,副反应为皮疹2例,均为1级。[结论]肺鳞癌患者EGFR基因突变率与性别和吸烟史相关,女性、不吸烟者EGFR突变率高于男性、吸烟者。EGFR-TKIs对EGFR敏感突变的肺鳞癌患者具有一定临床疗效,副反应可耐受。
[Objective] To investgate the status of epidermal growth factor receptor(EGFR) gene mutations in squamous cell carcinoma of lung(SCC) and the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) in EGFR mutationpositive SCC. [Methods] Clinical data of 172 patients with SCC admitted in Guangxi Medical University Affiliated Tumor Hospital from November 2013 to August 2017 were retrospectively analyzed. The mutations of EGFR gene were tested by amplification refractory mutation system(ARMS) method. Patients with positive EGFR mutation were treated with EGFRTKIs. [Results] Among 172 patients,15 cases were EGFR mutation positive(8.7%). The EGFR mutation rates in female and non-smokers were higher than those in male and smokers(22.2% vs. 5.1%,16.7% vs. 4.5%,P =0.001,0.007,respectively). EGFR mutation was not correlated with pathological grades,stages,specimen types and level of carcino-embryonic antigen(CEA) and squamous cell carcinoma antigen(SCC)(P>0.05). Five EGFR positive cases were treated with EGFR-TKIs as first-line therapy and 1 case treated as second-line therapy. The objective response rate was 33.3%,the disease control rate was 83.3%,median progression-free survival was 4.9 months,median overall survival was 10.75 months. Grade 1 skin rashes were observed in 2 cases. [Conclusion] EGFR mutation rate in lung SCC is related to gender and smoking status. EGFR-TKIs show clinical efficacy in EGFR mutationpositive patients with acceptable and tolerable adverse reactions.
[Objective] To investgate the status of epidermal growth factor receptor(EGFR) gene mutations in squamous cell carcinoma of lung(SCC) and the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) in EGFR mutationpositive SCC. [Methods] Clinical data of 172 patients with SCC admitted in Guangxi Medical University Affiliated Tumor Hospital from November 2013 to August 2017 were retrospectively analyzed. The mutations of EGFR gene were tested by amplification refractory mutation system(ARMS) method. Patients with positive EGFR mutation were treated with EGFRTKIs. [Results] Among 172 patients,15 cases were EGFR mutation positive(8.7%). The EGFR mutation rates in female and non-smokers were higher than those in male and smokers(22.2% vs. 5.1%,16.7% vs. 4.5%,P =0.001,0.007,respectively). EGFR mutation was not correlated with pathological grades,stages,specimen types and level of carcino-embryonic antigen(CEA) and squamous cell carcinoma antigen(SCC)(P>0.05). Five EGFR positive cases were treated with EGFR-TKIs as first-line therapy and 1 case treated as second-line therapy. The objective response rate was 33.3%,the disease control rate was 83.3%,median progression-free survival was 4.9 months,median overall survival was 10.75 months. Grade 1 skin rashes were observed in 2 cases. [Conclusion] EGFR mutation rate in lung SCC is related to gender and smoking status. EGFR-TKIs show clinical efficacy in EGFR mutationpositive patients with acceptable and tolerable adverse reactions.
引文
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[7]Zhang TT,Li JL.To analyze the clinicopathological features and prognosis of patients with lung squamous cell carcinoma with driver gene mutation[J].Chinese Journal of Lung Cancer,2016,19(10):648-652.[张童童,李峻岭.存在驱动基因突变肺鳞癌患者的临床病理特征及预后分析[J].中国肺癌杂志,2016,19(10):648-652.]
[2]Cheng F,Wang J,Chen J,et al.Effect of erlotinib on 34patients with lung squamous cell carcinoma[J].Chinese Journal of Lung Cancer,2016,19(10):679-681.[程芳,王静,陈洁,等.厄洛替尼治疗34例肺鳞癌患者的疗效观察[J].中国肺癌杂志,2016,19(10):679-681.]
[3]Hata A,Katakami N,Yoshioka H,et al.How sensitive are epidermal growth factor receptor-tyrosine kinase inhibitors for squamous cell carcinoma of the lung harboring EGFRgene-sensitive mutations?[J].J Thorac Oncol,2013,8(1):89-95.
[4]Joshi A,Zanwar S,Noronha V,et al.EGFR mutation in squamous cell carcinoma of the lung:does it carry the same connotation as in adenocarcinomas?[J].Oncol Targets Ther,2017,10:1859-1863.
[5]Cho SH,Park LC,Ji JH,et al.Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma NSCLC patients with EGFR mutation[J].Cancer Chemother Pharmacol,2012,70(2):315-320.
[6]Zhang Q,Zhu L.Epidermal growth factor receptor gene mutation status in pure squamous-cell lung cancer in Chinese patients[J].BMC Cancer,2015,15:88.
[7]Zhang TT,Li JL.To analyze the clinicopathological features and prognosis of patients with lung squamous cell carcinoma with driver gene mutation[J].Chinese Journal of Lung Cancer,2016,19(10):648-652.[张童童,李峻岭.存在驱动基因突变肺鳞癌患者的临床病理特征及预后分析[J].中国肺癌杂志,2016,19(10):648-652.]