For a study, researchers sought to evaluate the viability of cfDNA-based EGFR mutation testing as a monitoring tool for NSCLC patients. Patients with NSCLC carrying EGFR mutations and undergoing standard first-line therapy were included. EGFR mutation status was evaluated using baseline and post-treatment plasma samples. Patients whose EGFR mutation was found or maintained after the commencement of treatment were deemed to have circulating tumor DNA (ctDNA). The primary endpoints were progression-free survival (PFS) and overall survival (OS) for ctDNA-positive and negative patients following treatment initiation; the secondary endpoints were concordance for baseline EGFR status between tissue and plasma and proportion of ctDNA-positive patients following treatment initiation. 158 individuals were enrolled; 76 received gefitinib, and 82 received gefitinib with chemotherapy. The median period of follow-up was 42 months. Approximately 25% of patients were ctDNA-positive following the commencement of treatment. After therapy began, the median PFS for ctDNA-negative patients was 14 (95% CI, 12.0-17.0) months, whereas it was 8 (95% CI, 6.0-10.0) months for ctDNA-positive patients. After therapy initiation, the median OS for ctDNA-negative patients was 27 (95% CI, 24.0-32.0) months, whereas it was 15 (95% CI, 11.0-19.0) months for ctDNA-positive patients. The baseline concordance between tissue and plasma samples was 75.4%. After treatment commencement, detection of EGFR mutations in plasma could be utilized as a predictive diagnostic in patients with EGFR-mutant NSCLC receiving first-line therapy.