Data from Exosome-Based Detection of <i>EGFR</i> T790M in Plasma from Non–Small Cell Lung Cancer Patients

Abstract

<div>Abstract<p><b>Purpose:</b> About 60% of non–small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the <i>EGFR</i> T790M mutation. Patients with this mutation respond well to third-generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a noninvasive option to detect the mutation; however, sensitivity is low as many patients have too few detectable copies in circulation. Here, we have developed and validated a novel test that overcomes the limited abundance of the mutation by simultaneously capturing and interrogating exosomal RNA/DNA and cfDNA (exoNA) in a single step followed by a sensitive allele-specific qPCR.</p><p><b>Experimental Design:</b> ExoNA was extracted from the plasma of NSCLC patients with biopsy-confirmed T790M-positive (<i>N</i> = 102) and T790M-negative (<i>N</i> = 108) samples. The T790M mutation status was determined using an analytically validated allele-specific qPCR assay in a Clinical Laboratory Improvement Amendment laboratory.</p><p><b>Results:</b> Detection of the T790M mutation on exoNA achieved 92% sensitivity and 89% specificity using tumor biopsy results as gold standard. We also obtained high sensitivity (88%) in patients with intrathoracic disease (M0/M1a), for whom detection by liquid biopsy has been particularly challenging.</p><p><b>Conclusions:</b> The combination of exoRNA/DNA and cfDNA for T790M detection has higher sensitivity and specificity compared with historical cohorts using cfDNA alone. This could further help avoid unnecessary tumor biopsies for T790M mutation testing. <i>Clin Cancer Res; 24(12); 2944–50. ©2018 AACR</i>.</p></div>