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EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6.

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机构: [1]Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou 510080, China [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 [9]West German Cancer Center, University Duisburg-Essen, Hufelandstraβe 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, Montreal, 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
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关键词: afatinib circulating cell-free DNA ErbB family blocker EGFR mutation non-small cell lung cancer

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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.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 2 区 肿瘤学
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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
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通讯机构: [1]Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan 2nd Road, Guangzhou 510080, China [18]National Taiwan University Hospital, 7 Chung- Shan South Road, Taipei 100, Taiwan
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