中国东北地区肺癌患者EGFR复合突变的真实世界研究

A real-world study on compound EGFR mutations in northeast China patients with lung adenocarcinoma

目的表皮生长因子受体(EGFR)是中国非小细胞肺癌(NSCLC)患者中最常见的突变驱动基因。EGFR-酪氨酸激酶抑制剂(TKI)已成为晚期NSCLC的标准治疗方案。小样本量的回顾性研究报道,复合EGFR突变状态与EGFR-TKI治疗的不同疗效相关。本研究旨在探讨东北地区肺癌患者EGFR复合突变的临床相关因素及EGFR治疗效果。方法2013年5月-2022年5月在吉林省肿瘤医院采用扩增阻滞突变系统PCR(ARMS-PCR)检测EGFR基因突变的患者。根据突变类型将复合突变分为3组:常见型(19del+L858R)、耐药型(T790M或20ins)和罕见型。以单基因突变患者为对照,分析临床病理特征及EGFR-TKI疗效。结果共纳入4768例肺腺癌病例,其中单基因突变患者1930例(40.48%),复合突变患者166例(3.48%)。常见、耐药和罕见型复合突变的患病率分别为18.07%(30例)、62.05%(103例)和19.88%(33例)。四组患者年龄、性别、脑转移、PS评分差异无统计学意义(P>0.05),吸烟情况差异有统计学意义(P=0.020)。常见型复合突变、耐药型复合突变、罕见型复合突变和单基因突变EGFR-TKI反应率(RR)分别为63.6%(7/11)、27.3%(3/11)、0(0/6)、70.6%(12/17),四组临床获益率(CBR)分别为81.8%(9/11)、90.9%(10/11)、50.0%(3/6)、94.1%(16/17)。中位无进展生存期(PFS)分别为7.3个月、5个月、3.5个月和14.5个月,四组间差异均有统计学意义(P<0.001)。结论不同的复合突变状态与EGFR-TKI的治疗效果相关。常见型治疗效果最好,耐药型最差,提示准确的分子诊断和进一步的基因突变分类对指导靶向治疗至关重要。

Objective Epidermal growth factor receptor(EGFR)is the most common mutation driver gene in Chinese patients with non-small cell lung cancer(NSCLC).EGFR-tyrosine kinase inhibitors(TKI)have become standard treatment for advanced NSCLC.Retrospective studies of small sample size reported that compound EGFR mutation status was related to diverse efficacy of EGFR-TKI treatment.This study aimed to explore the clinical factors related to compound EGFR mutations and efficacy of EGFR treatment from northeast Chinese patients with adenocarcinoma.Methods EGFR was detected by amplification refractory mutation system(ARMS)-PCR in Jilin cancer hospital from May 2013 to May 2022.According to the prevalence,the compound mutations were divided into 3 groups:the common type group(19del+L858R),the drug-resistant type group(T790M or 20ins)and the rare type group.Clinicopathological characteristics and EGFR-TKI efficacy were analyzed,and the patients with single mutation were set as the control group.Conclusion A total of 4768 lung adenocarcinoma cases were enrolled,including 1930(40.48%)single mutation cases and 166(3.48%)compound mutation cases.The prevalence of common,drug-resistant and rare compound mutation was 18.07%(n=30),62.05%(n=103)and 19.88%(n=33),respectively.No significant difference was found among the four groups regarding to age,gender,brain metastasis and PS score(P>0.05),but there was a statistical difference in smoking status(P=0.020).The EGFR-TKI response rate(RR)of the common,drug-resistant,rare,and control groups was 63.6%(7/11),27.2%(3/11),0%(0/6),and 70.6%(12/17),respectively,and the clinical benefit rate(CBR)in the four groups was 81.8%(9/11),90.9%(10/11),50%(3/6),and 94.1%(16/17),respectively.The median progression free survival(PFS)were 7 months,4 months,3 months and 14 months respectively,and the differences among the four groups were statistically significant(P<0.001).Conclusion Different compound mutation status is associated with therapeutic efficacy of EGFR-TKI.Common type has the best therapeutic effect,while resistant type has the worst,suggesting that accurate molecular diagnosis and further genetic mutation classification are crucial to guide targeted therapy.