Background: 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.

Citation： Wu Yi-Long, Sequist Lecia V., Hu Cheng-Ping, Feng Jifeng, Lu Shun, Huang Yunchao, Li Wei, Hou Mei, Schuler Martin, Mok Tony, Yamamoto Nobuyuki, O'Byrne Kenneth, Hirsh Vera, Gibson Neil, Massey Dan, Kim Miyoung, Yang James Chih-Hsin. EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6. West China medical Virtual Journal, 2000, 1(1): 175-185-. doi: 10.1038/bjc.2016.420 Copy