机构：[1]Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou 510080, China广东省人民医院[2]Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA[3]Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410018, China[4]Jiangsu Provincial Tumor Hospital, 42 Baiziting, Xuanwu, Nanjing, Jiangsu 210009, China[5]Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Xuhui, Shanghai 200030, China[6]Yunnan Tumor Hospital (The Third Affiliated Hospital of Kunming Medical University), Xingjie Alley, Xishan, Kunming, Yunnan, China[7]Cancer Center, First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China[8]West China Hospital, Sichuan University, 24 South Section 1, Yihuan Road, Chengdu, 610065, China四川大学华西医院[9]West German Cancer Center, University Duisburg-Essen, Hufelandstrae 55, Essen 45147, Germany[10]German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen 45147, Germany[11]The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China[12]Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama Prefecture 641- 8509, Japan[13]Princess Alexandra Hospital and Queensland University of Technology, 199 Ipswich Road, Woolloongabba, QLD 4102, Australia[14]McGill University, 845 Rue Sherbrooke O, Montre´ al, QC H3A 0G4, Canada[15]Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Street 65, Biberach 88400, Germany[16]Boehringer Ingelheim Ltd UK, Ellesfield Avenue, Bracknell, Berkshire RG12 8YS, UK[17]Boehringer Ingelheim GmbH, Binger Street 173, Ingelheim 55216, Germany[18]National Taiwan University Hospital, 7 Chung- Shan South Road, Taipei 100, Taiwan
In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+).
Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit.
EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P<0.0001) and cfDNA- (LL3: HR, 0.46; P<0.0001; LL6: HR, 0.12; P<0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients.
Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status.
基金：
Medical writing assistance, supported financially by Boehringer
Ingelheim, was provided by Katie McClendon, PhD, of GeoMed,
an Ashfield business, part of UDG Healthcare plc, during the
preparation of this article. The authors were fully responsible for all
content and editorial decisions, were involved at all stages of
manuscript development, and have approved the final version.
This study was supported by Boehringer Ingelheim.
第一作者机构：[1]Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou 510080, China
通讯作者：
推荐引用方式(GB/T 7714)：
Yi-Long Wu,Lecia V Sequist,Cheng-Ping Hu,et al.EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6.[J].BRITISH JOURNAL OF CANCER.2017,116(2):175-185.doi:10.1038/bjc.2016.420.
APA：
Yi-Long Wu,Lecia V Sequist,Cheng-Ping Hu,Jifeng Feng,Shun Lu...&James Chih-Hsin Yang.(2017).EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6..BRITISH JOURNAL OF CANCER,116,(2)
MLA：
Yi-Long Wu,et al."EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6.".BRITISH JOURNAL OF CANCER 116..2(2017):175-185
医学