P3.02a-030 ROS1 Fusion Chinese Lung Adenocarcinoma Patients Treated with Crizotinib Detected Using Next-Generation Genotyping from ctDNA: Topic: ROS1

Abstract

Chromosomal rearrangements involving the c-ros oncogene 1 (ROS1) have been described as a subset of non-small cell lung cancer (NSCLC). Recently Crizotinib has exhibited marked therapeutic efficacy in the treatment of the ROS1 fusion NSCLC. However, resistance often occurs and repeated biopsy is necessary for tumor genotyping and underlying resistant mechanism. Circulating tumor DNA (ctDNA) represents a promising way to assess tumor genetic profile non-invasively. This study aims to assess whether liquid biopsies accurately screen disease diagnosis and reflect the response to Crizotinib treatment through analysis of ctDNA for ROS1 fusions in patients with lung adenocarcinoma, and to elucidate the underlying mechanisms of ROS1 targeted drug resistance. Twelve plasma samples were collected from a cohort of 4 patients with ROS1 fusion advanced stage lung adenocarcinoma, confirmed by fluorescent in situ hybridization (FISH) in tissue. A prospective-retrospective analysis on ctDNA was further performed from archived plasma samples using our ctDNA panel with concurrent CT or MRI imaging at the baseline and 8-week intervals during responsive Crizotinib treatment, and at progressive disease. All patients showed detectable levels of ROS1 fusion in ctDNA at baseline. Upon treatment with Crizotinib, response rate is inversely correlated with levels of ROS1 fusion. One patient with progressive disease, patient 1, exhibited a detectable CD74-ROS1 fusion with 13.5% concentration at baseline; it was undetectable at partial response and re-elevated to 8.2% accompanied by an acquired G2032R mutation when disease progressed. Our ctDNA panel could be applied clinically to detect ROS1 fusion from plasma for accurate screening and convenient monitoring where detection correlates with disease status, and could distinguish mutations associated with Crizotinib induced resistance in patients with NSCLC, thus facilitating personalized cancer therapy.