Wu, Yi-LongSequist, LeciaHu, Cheng-PingFeng, JifengLu, ShunHuang, YunchaoLi, WeiHou, MeiSchuler, MartinMok, TonyYamamoto, NobuyukiO'Byrne, KennethHirsh, VeraGibson, NeilMassey, DanKim, MiyoungYang, James Chih-Hsin2017-02-182017Wu, Y., L. V. Sequist, C. Hu, J. Feng, S. Lu, Y. Huang, W. Li, et al. 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): 175-185. doi:10.1038/bjc.2016.420. http://dx.doi.org/10.1038/bjc.2016.420.0007-0920http://nrs.harvard.edu/urn-3:HUL.InstRepos:30370933Background: 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+). Methods: 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. Results: 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. Conclusions: 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.en-USafatinibcirculating cell-free DNAErbB family blockernon-small cell lung cancerJournal Article2017-02-1810.1038/bjc.2016.420