JCES01.09 A Comparison of ddPCR and ARMS for Detecting EGFR T790M Status from Advanced NSCLC Patients with Acquired EGFR-TKI Resistance

Abstract

To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy. To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy. To assess the ability of droplet digital PCR and ARMS technology to detect epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance. A sensitive and convenient method for detecting T790M mutation would be desirable to direct patient sequential treatment strategy. A total of 108 patients were enrolled in this study. 108 patient plasma samples were detected by ddPCR and 75 were detected by ARMS. And 16 patients experienced re-biopsy were detected T790M status by ARMS method. 43.7% (47/108) had acquired T790M mutation by ddPCR. In 75 patient plasma samples, comparing ddPCR with ARMS, the rates of T790M mutation were 46.7% (35/75) and 25.3% (19/75) by ddPCR and ARMS, respectively. Of all, 16 patients both had tumor and plasma samples, the T790M mutation rates were 56.3% (9/16) by ARMS in tissue and 50.5% (8/16) by ddPCR in plasma ctDNA. Among them, there were two ctDNA T790M mutations by ddPCR but T790M gene negative in tumor tissue by ARMS method. For all patients, the median PFS and OS were 12.3 months and 32.8 months, respectively. The patients with T790M-positive tumors had a longer time to disease progression after treatment with EGFR-TKIs (median, 13.1 months vs 10.8 months; P=0.010) and overall survival (median, 35.3 months vs 30.3 months; P=0.214) compared with those with T790M-negative patients. Our study demonstrates dPCR assay provide feasibility and sensitive method in detecting EGFR T790M status in plasma samples from NSCLC patients with acquired EGFR-TKI resistance.And T790M-positive patients have better clinical outcomes to EGFR-TKIs than patients with T790M negative.