Abstract 4178: Circulating cell-free DNA in plasma of never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as a first-line therapy

Abstract

Abstract Background: Circulating cell-free DNA (CFDNA) has been investigated as a potential screening or prognostic marker in a variety of cancers, including lung cancers. This study aimed to investigate prospectively its clinical significance in never smokers with advanced lung adenocarcinoma (ALAC) undergoing chemotherapy. Methods: We analyzed blood samples of 134 patients among 309 never smokers with ALAC who were enrolled to a prospective randomized phase III study comparing gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy from April 2005 to November 2007 (the First-SIGNAL). An amount of plasma CFDNA was measured by real-time quantitative polymerase chain reaction targeting human β-actin genomic sequence. Results: Median baseline CFDNA value was 122.3 ng/ml (range, 11.5 to 2487.9 ng/ml). Patients with > 2 of metastatic sites had higher plasma CFDNA compared those with ≤ 2 metastatic sites (P = 0.015). Baseline plasma CFDNA was positively associated with peak standardized uptake value of primary tumor on 18F-FDG PET (coefficient = 0.316; P = 0.056). In GP arm, high CFDNA group showed higher response rate (RR) than low CFDNA group (60.7% vs. 37.8%; P = 0.047). However, in gefitinib arm, no difference was observed in RR between the two groups (47.2% vs. 58.1%; P = 0.376). The risk of death was elevated with increasing baseline plasma CFDNA [hazard ratio (HR) = 1.23; 95% CI, 1.01-1.50; P = 0.045)]. The low tertile group of baseline CFDNA showed longer overall survival (OS) than the high tertile group [HR of low vs. high groups = 0.52 (95% CI, 0.31-0.87); median OS, 28.6 vs. 16.0 months; P = 0.041]. Conclusion: High plasma CFDNA at diagnosis predicts an aggressive behavior and poor survival outcomes in these patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4178. doi:10.1158/1538-7445.AM2011-4178