Comparison of different methods for detecting epidermal growth factor receptor mutations in peripheral blood as a predictor of response to gefitinib.

Abstract

10557 Background: Several studies have reported the detection of active EGFR mutation DNA in peripheral blood can also predict the response to EGFR-TKI in NSCLC. But heterogeneity in methodologies makes it difficult to use in daily practice. Goal of this study is to compare different methods for detecting EGFR mutation DNA in peripheral blood. Methods: From July 2007 to April 2009, fifty-one advanced NSCLC patients with pairs of tumour and serum samples treated with gefitinib were included. Response was evaluated by RECIST criteria. EGFR mutations in tumor tissues were detected by Scorpions-Amplification Refractory Mutation System (Scorpions-ARMS). Three methods were used to detect the mutations DNA in peripheral blood: denaturing high performance liquid chromatography (DHPLC), Mutant-Enriched-Liquidchip (ME-Liquidchip) and Scorpions-ARMS. Results: The Objective response rates (ORR) in whole group patients are 33.3% (17/51). EGFR Mutation rate were identified 15.7% (8/51), 27.5% (14/51), 29.4% (15/51) by DHPLC, ME-Liquidchip, Scorpions-ARMS in peripheral blood respectively. Only 34 cases were available for paired tumor sample EGFR mutation detection. In these 34 patients, EGFR mutation rate in tumor tissue was 41.2% (14/34). The corresponding rates of EGFR mutation status in peripheral blood with tumor tissues are 58.8% (by DHPLC), 58.8% (by ME-Liquidchip) and 70.6% (by Scorpions-ARMS). The ORRs by different method of EGFR mutation detection were 71.4% (Tumor sample), 62.5% (Blood DHPLC), 50.0% (Blood, ME-Liquidchip) and 66.7% (Blood, Scorpions-ARMS). EGFR Mutation detected by Scorpions-ARMS in tumor tissues and peripheral blood have a better prediction of ORR of EGFR-TKI (p=0.002 and p=0.003) compare DHPLC and ME-Liquidchip method. Conclusions: Tumor tissue is the better source of samples to detect EGFR mutation of NSCLC patients than peripheral blood. Scorpions-ARMS method is superior to DHPLC and ME-Liquidchip in serum EGFR mutation DNA detection. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Innovation Centre China, R&D AstraZeneca, Surexam, Inc AstraZeneca, GlaxoSmithKline AstraZeneca, Bayer, Novartis, sanofi-aventis