P3.02a-011 Analysis of ALK Status in Peripheral Blood to Predict the Clinical Activity of Alk Inhibitors and Assess Prognosis in Patients with Lung Cancer: Topic: ALK Biomarkers

Abstract

Gene fusion of EML4-ALK and gene mutation in ALK kinase domain are important determinants of the response of targeted therapy in lung cancer. In this study, Droplet Digital PCR (ddPCR) were used to assess the ALK gene status of blood-based nucleic acid, to develop a non-invasive assessment for treatment and progresses of lung cancer. Three FFPE samples and 17 peripheral blood samples were collected from 11 patients with lung cancer, 5 of which were detected 2 – 5 times following their treatments. ddPCR technology were used to identify rearrangement of EML4-ALK in RNA from the peripheral blood samples and FFPE samples, and mutations in ALK kinase domain from 12 of the 17 peripheral blood. Correlation of responses to ALK inhibitors and progress in tumor based on ALK gene status were analyzed. Rearrangement of EML4-ALK were detected in all the 3 (100%) FFPE samples, and 2 of 4 (50%) blood samples by ddPCR in initial. Gene mutations including L1152R, C1156Y, F1174L, L1196M, D1203N and G1269A in ALK kinase domain were detected in 10 of 12 (88.3%) blood samples after ALK inhibitors treatment. L1152R and D1203N were detected more frequent (29.6% for both), and other 4 mutations were detected a frequency of 3.7%. For most patients detected more than 1 time, the abundance of EML4-ALK, L1152R and D1203N were found decreased after ALK inhibitors treatment (Fig. 1). LDK378 were used after resistance to crizotinb developed in patients BMS, ZQ and HSR. C1156Y, which interferes drug binding, were found in patients BMS and ZQ who showed poor response to LDK378 treatment; whereas L1196M, which enhances drug binding, was found in patient HSR who showed good response to LDK378. ALK gene status in peripheral blood detecting by ddPCR could be a viable approach for non-invasive analysis of tumor genotype in real time.