Abstract 663: Longitudinal AXL assessment of circulating tumor cells (CTCs) and its clinical implication in the patients with EGFR mutated non-small cell lung cancer (NSCLC)

Abstract

Abstract Gefitinib for EGFR mutated non-small cell lung cancer (NSCLC) is showing acquired resistance after 8-11 months, and about 60% of its mechanisms have been reported due to T790M mutation. In about a third of NSCLC, AXL expression can be observed at baseline status. And because AXL expression could be a mechanism of drug resistance, we decided to monitor AXL expression before and after Gefitinib treatment in EGFR mutated NSCLC patients through circulating tumor cells (CTCs). Herein, Thirty-seven out of 55 participants who showed acquired resistance to EGFR-TKI were selected in this prospective analysis. To evaluate the AXL expression on the CTCs, serial blood was obtained (tracking for 4, 12, 24 and 36 weeks after EGFR-TKIs). Baseline tumor tissues were also obtained for genetic analysis. Progression-free survival (PFS) and overall survival (OS) were explored according to the baseline AXL expression. AXL expression was analyzed by observation and quantitative intensity-dependent fold change analysis using immunofluorescence analysis. CTCs were isolated and analyzed by CytoGen's Smart Liquid Biopsy platform that uses the size-based gravity filtration for CTC isolation. We found out that there were ten cases (27%) of the increasing pattern of AXL expression in CTCs during longitudinal monitoring in patients with progressive disease (PD). The most remarkable aspect is that AXL up-regulation in CTCs preceded the time point of clinical PD. These results imply that the expectation of clinical PD by blood CTC (liquid biopsy-based examination) can be combined with the T790M. Moreover, the PFS (p= 0.002) and OS (p= 0.007) were both worse in patients with AXL expression at the baseline status compared with patients without AXL expression (N=55). Conclusively, this study implicates that AXL in CTCs could be deployed for prognostic evaluation. And the clinical monitoring of specific target marker in CTC could help for further treatment strategy. Citation Format: Mi Young Choi, Da Hye Moon, Hae Ung Lee, Jong Min Jo, Young Woong Sohn, Byung Hee Jeon, Sang-We Kim. Longitudinal AXL assessment of circulating tumor cells (CTCs) and its clinical implication in the patients with EGFR mutated non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 663.