Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR‐TKI treatment in advanced non‐small cell lung cancer

BACKGROUND: Circulating tumor DNA (ctDNA) has made a breakthrough as an early biomarker in operable early‐stage cancer patients. However, the function of ctDNA combined with cell‐free DNA (cfDNA) as a predictor in advanced non‐small cell lung cancer (NSCLC) remains unknown. Here, we explored its potential as a biomarker for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in patients with advanced NSCLC. METHODS: A retrospective analysis was undertaken. Plasma collected from 51 patients with advanced NSCLC prior to and serially after starting treatment with EGFR‐TKIs was analyzed by next‐generation sequencing (NGS). The performance of ctDNA, cfDNA, and combining ctDNA with cfDNA were evaluated for their ability to predict survival outcomes. RESULTS: Patients with early undetectable ctDNA and increasing cfDNA had a markedly better progression‐free survival (PFS) (p < 0.001) and overall survival (OS) (p = 0.001) than those with early detectable ctDNA and decreasing cfDNA. Patients with early ctDNA clearance were more likely to have the ctDNA persistent clearance (p = 0.006). The early clearance rate of ctDNA in the normal carcinoembryonic antigen (CEA) group was significantly higher than in the low and high groups (p = 0.028). Patients with greater CEA decline had a higher early clearance rate of ctDNA than those with minor CEA change (p = 0.016). CONCLUSIONS: We based this study on ctDNA and cfDNA, explored its prognostic predictive ability, and combined CEA to monitor EGFR‐TKI efficacy. This study may provide new perspectives and insights into the precise treatment strategies for NSCLC patients.