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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2021年02期

页码:

169-173

栏目:

论著

出版日期:

2021-04-20

文章信息/Info

Title:

Distribution characteristics of plasma EGFR T790M mutation in patients with advanced NSCLC treated with three first-generation EGFR-TKIs

作者:

付光明 刘 平 吴 芳 向晓康 胡春宏 刘先领 熊 慧

410011 长沙,中南大学湘雅二医院肿瘤科

Author(s):

Fu Guangming;  Liu Ping;  Wu Fang;  Xiang Xiaokang;  Hu Chunhong;  Liu Xianling;  Xiong Hui.

Department of oncology, the Second Xiangya Hospital of Central South University, Changsha410011, China

关键词:

表皮生长因子受体-酪氨酸激酶抑制剂;  血液;  T790M突变;  晚期非小细胞肺癌

Keywords:

EGFR-TKI;  blood T790M mutation;  Mutation rate;  Advanced non-small cell lung cancer

分类号:

R734.2

DOI:

10.3877/cma.j.issn.1674-6902.2021.02.007

摘要:

目的 探究真实世界中表皮生长因子受体(EGFR)敏感突变的晚期NSCLC患者使用吉非替尼、厄洛替尼、埃克替尼一线治疗进展后T790M突变的分布特征。方法 2017年6月至2019年6月期间557例肺癌患者,145例经病理组织学或细胞学确诊为晚期非小细胞肺癌(NSCLC)且具有EGFR敏感突变的患者,给予吉非替尼、厄洛替尼、埃克替尼一线治疗。随访进展后,采集其外周血10 ml,利用Super-ARMS法检测T790M突变。通过χ²检验,Kaplan-Meier分析,回顾性分析晚期NSCLC患者接受吉非替尼、厄洛替尼、埃克替尼一线治疗后 T790M突变患者的分布特征。 结果 回顾性分析的145例患者,56例一线接受吉非替尼治疗,16例接受厄洛替尼治疗,73例接受埃克替尼治疗。Super-ARMS检测结果显示,一代EGFR-TKIs治疗进展后T790M突变的总体发生率为 40%(58/145),其中吉非替尼组41.07%(23/56)、厄洛替尼组31.25%(5/16)、埃克替尼组41.10%(30/73)。三组患者之间T790M突变的发生率无统计学差异。但是,肺腺癌(P=0.0001)及初始EGFR突变为19del(P=0.0014)的患者更易发生T790M突变。 T790M阳性患者中,吉非替尼、厄洛替尼、埃克替尼的中位PFS(mPFS)分别为:11个月、18个月和12个月,组间无统计学差异。TKI治疗1年、2年后T790M突变率及T790M阳性人群的中位PFS均无统计学差异。结论 真实世界中吉非替尼、厄洛替尼、埃克替尼一线治疗晚期NSCLC耐药进展后,其血检标本T790M的突变发生率无统计学差异。但是,初始突变为19del的患者相较于L858R突变的患者更容易发生T790M突变。这也进一步预示着NSCLC患者精细化管理的必要性。

Abstract:

Objective The purpose of this study is to study the distribution characteristics of T790M mutations in advanced NSCLC patients with epidermal growth factor receptor(EGFR)-sensitive mutations in the real world after receiving first-line treatment with three different generations of EGFR-TKIs. Methods Between June 2017 and June 2019, a total of 557 patients with NSCLC were enrolled in this study. 145 patients with advanced non-small cell lung cancer(NSCLC)diagnosed with histopathology or cytology with EGFR-sensitive mutations were randomized to gefitinib, erlotinib, icotinib first-line treatment. By χ² test, Kaplan-Meier method, retrospectively analyze the probability of acquiring T790M after taking first-line TKIs(gefitinib, Erlotinib, icotinib)and clinical features of patients with T790M mutation. Results Of the 557 patients screened, 145 fulfilled the inclusion criteria and were enrolled in this retrospective analysis. In these patients, 56 patients received gefitinib in the first line, 16 received erlotinib, and 73 received icotinib. Super-ARMS test results showed that the overall incidence of T790M mutation was 40%(58/145), including 41.07%(23/56)in the gefitinib group and 31.25 in the erlotinib group%(5/16), 41.10%(30/73)in the icotinib group. There was no statistical difference in the incidence of T790M mutation among the three groups. However, patients with lung adenocarcinoma(P=0.0001)and patients with an initial EGFR mutation of 19del(P=0.0014)had a higher frequency of T790M mutations. Among the T790M positive population, the median PFS of gefitinib, erlotinib and ectinib was: 11, 18 and 12 m. The 1-year and 2-year detection rates of T790M mutation were 6.25%, 29.09%, 24.66% and 31.24, 45.45% and 41.09%, no statistical difference between the groups. Conclusion There was no significant difference in the incidence of T790M mutation among the advanced NSCLC treatment with first-generation EGFR-TKI. In the T790M positive population, the median PFS and the 1-year and 2-year detection rates of T790M mutation were no statistical difference between the groups. This further indicates the necessity of refined management of NSCLC patients.

参考文献/References:

1 钱桂生. 肺癌不同病理类型发病率的变化情况及其原因[J/CD]. 中华肺部疾病杂志(电子版), 2011, 4(1): 1-5.
2 Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin,2016, 66(2): 115-132.
3 Morgillo F, Della Corte CM, Fasano M, et al. Mechanisms of resistance to EGFR-targeted drugs: lung cancer[J]. ESMO Open, 2016, 1(3): e000060.
4 Lim SM, Syn NL, Cho BC, et al. Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies[J]. Cancer Treat Rev, 2018, 65: 1-10.
5 中国临床肿瘤学会肿瘤生物标志物专家委员会,《中国非小细胞肺癌患者EGFRT T790M基因突变检测专家共识》制定专家组. 中国非小细胞肺癌患者EGFR T790M基因突变检测专家共识[J]. 中华医学杂志, 2018, 98(32): 2544-2551.
6 Cardona AF, Arrieta O, Zapata MI, et al. Acquired resistance to Erlotinib in EGFR mutation-positive lung adenocarcinoma among hispanics(CLICaP)[J]. Target Oncol, 2017, 12(4): 513-523.
7 Ettinger DS, Wood DE, Aggarwal C, et al. NCCN guidelines insights: Non-small cell lung cancer, version 1.2020[J]. J Natl Compr Canc Netw, 2019, 17(12): 1464-1472.
8 Gao J, Li HR, Jin C, et al. Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer[J]. Clin Transl Oncol, 2019, 21(10): 1287-1301.
9 Jia Y, Yun CH, Park E, et al. Overcoming EGFR(T790M)and EGFR(C797S)resistance with mutant-selective allosteric inhibitors[J]. Nature, 2016, 534(7605): 129-132.
10 Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumours: learning from lung cancer[J]. Nat Rev Clin Oncol, 2014, 11(8): 473-481.
11 Yu JY, Yu SF, Wang SH, et al. Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21 [J]. Chin J Cancer, 2016, 35: 30.
12 曹紫阳, 吴 伟, 候立坤, 等. 微滴数字PCR与Super-ARMS+PCR检测非小细胞肺癌患者表皮生长因子受体(EGFR)酪氨酸激酶[J]. 中华病理学杂志, 2018, 47: 910-914.
13 石岳泉, 杨向红. 非小细胞肺癌的驱动基因及其临床意义[J]. 中国肺癌杂志, 2014, 17(6): 481-486.
14 Lee CK, Kim S, Lee JS, et al. Next-generation sequencing reveals novel resistance mechanisms and molecular heterogeneity in EGFR-mutant non-small cell lung cancer with acquired resistance to EGFR-TKIs[J]. Lung Cancer, 2017, 113: 106-114.
15 Lee DH. Treatments for EGFR-mutant non-small cell lung cancer(NSCLC): The road to a success, paved with failures[J]. Pharmacol Ther, 2017, 174: 1-21.
16 Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors[J]. Sci Transl Med, 2011, 3(75): 75ra26.
17 Oya Y, Yoshida T, Kuroda H, et al. Association between EGFR T790M status and progression patterns during initial EGFR-TKI treatment in patients harboring EGFR mutation [J]. Clin Lung Cancer, 2017, 18(6): 698-705 e692.
18 Gao W, He J, Jin SD, et al. Association of initial epidermal growth factor receptor tyrosine kinase inhibitors treatment and EGFR exon 19 deletion with frequency of the T790M mutation in Non-small cell lung cancer patients after resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitors [J]. Onco Targets Ther, 2019, 12: 9495-9504.
19 Huang YH, Hsu KH, Tseng JS, et al. The Association of acquired T790M mutation with clinical characteristics after resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitor in lung adenocarcinoma[J]. Cancer Res Treat, 2018, 50(4): 1294-1303.
20 Lin YT, Chen JS, Liao WY, et al. Clinical outcomes and secondary epidermal growth factor receptor(EGFR)T790M mutation among first-line gefitinib, erlotinib and afatinib-treated non-small cell lung cancer patients with activating EGFR mutations [J]. Int J Cancer 2019, 144(11):2887-2896.
21 Nosaki K, Satouchi M, Kurata T, et al. Re-biopsy status among non-small cell lung cancer patients in Japan: A retrospective study[J]. Lung Cancer, 2016, 101: 1-8.
22 Joo JW, Hong MH, Shim HS. Clinical characteristics of T790M-positive lung adenocarcinoma after resistance to epidermal growth factor receptor-tyrosine kinase inhibitors with an emphasis on brain metastasis and survival[J]. Lung Cancer, 2018, 121: 12-17.
23 Su KY, Chen HY, Li KC, et al. Pretreatment epidermal growth factor receptor(EGFR)T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer[J]. J Clin Oncol, 2012, 30(4): 433-440.
24 Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase Ⅲ, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia(IPASS)[J]. J Clin Oncol, 2011, 29(21): 2866-2874.
25 Shi YK, Wang L, Han BH, et al. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma(CONVINCE): a phase 3, open-label, randomized study[J]. Ann Oncol, 2017, 28(10): 2443-2450.

备注/Memo

备注/Memo:

基金项目: 湖南省自然科学基金资助项目(No.2020JJ4817)
通信作者: 熊 慧, Email: xionghui3441@csu.edu.cn

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更新日期/Last Update: 2021-04-20