Abstract 597: Comprehensive analysis of blood-based biomarkers to immunotherapy using circulating tumor cells, peripheral blood cells and circulating tumor DNA in advanced non-small cell lung cancer

Abstract

Abstract Background: This study aimed to investigate the feasibility of liquid biopsy using circulating tumor cells (CTCs), peripheral blood cells (PBCs) and circulating tumor DNA (ctDNA) as predictive blood-based biomarkers to immunotherapy in advanced non-small cell lung cancer (NSCLC). Methods: This study included patients with advanced NSCLC receiving pembrolizumab or atezolizumab from July 2019 to June 2020. Blood was collected in K2-EDTA tube before each administration from cycle 1 to 4 (C1-4), and PBC counts (absolute neutrophil count[ANC], neutrophil-to-lymphocyte ratio[NLR], derived NLR[dNLR], platelet-to-lymphocyte ratio[PLR]) were calculated at each cycle. CTCs were enriched by using CD-PRIMETM system, the antibody-independent size-based isolation method, and identified by single positive cells (EpCAM/CK+CD45-) in BioViewCCBSTM system. Cell-free DNA was purified and extracted from plasma at baseline and C4 or end-of-treatment. Results: Among 83 response-evaluable patients, objective response rate was 19% and durable clinical benefit (DCB) were 34%. Baseline (C1) CTC, PBC count and ctDNA amount did not show a significant difference according to best response and DCB. However, patients with lower NLR, dNLR, PLR and ctDNA level at C1 showed significant benefit in progression-free survival (PFS) and overall survival (OS) (p<0.05 for all). Patients with decreased CTC at C2 compared to C1 showed benefit in median PFS (6.2 vs 2.3, p=0.078) and OS (not reached [NR] vs 6.8, p=0.021) than those with increased CTC count. Low dNLR (≤2.0) at C1 and decreased CTC at C2 compared to C1 were the independently significant factors for survival. Conclusion: Comprehensive analysis of CTC, PBC count and ctDNA amount at baseline and their changes during treatment could be potential biomarkers to predict the survival benefit and may help risk-group stratification in patients with advanced NSCLC who received anti-PD-1/PD-L1 immunotherapy. Citation Format: Cheol-Kyu Park, Hyun-Ju Cho, In-Jae Oh, Young-Chul Kim. Comprehensive analysis of blood-based biomarkers to immunotherapy using circulating tumor cells, peripheral blood cells and circulating tumor DNA in advanced non-small cell lung cancer [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 597.