EGFR mutation status in plasma and tumor tissues in non-small cell lung cancer serves as a predictor of response to EGFR-TKI treatment

Objective: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can effectively control non-small cell lung cancer (NSCLC). Therefore, EGFR mutations should be detected before lung cancer patients undergo EGFR-TKI therapy. This study assessed the feasibility and predictive value of EGFR mutations in peripheral blood samples. Methods: EGFR mutations in exons 19 and 21 were analyzed in tumor tissue and plasma DNA samples from 121 NSCLC patients using amplification refractory mutation system (ARMS) and the integrated technique of mutant enriched PCR (me-PCR) and denaturing high performance liquid chromatography (DHPLC), respectively. Results: EGFR mutations were detected in 36.4% of tumor tissues and 34.7% of the plasma at a concordance rate of 85.1% (103/121). The sensitivity and specificity of plasma EGFR mutations were 77.3% and 89.6%, respectively. The gender and tumor histology of patients served as independent predictors of EGFR mutations in both tumor tissues and plasma, while CEA level was an independent predictor of EGFR mutations in the plasma. Furthermore, EGFR-TKI treatment showed a significantly higher objective response rate (ORR), median progression-free survival (mPFS), and overall survival (mOS) in patients harboring EGFR mutation than those that did not exhibit EGFR mutation (ORR: 69.4% versus 13.0% in tissues, P < 0.001; 64.5 % vs. 28.6% in the plasma, P = 0.006. mPFS: 10.4 months versus 4.1 months in tissues, P<0.001; 10.5 months vs. 5.2 months in the plasma, P=0.001. mOS: 25.7 months versus 8.3 months in tissues, P=0.005; 25.7 months vs. 13.5 months in the plasma, P=0.038). Conclusions: EGFR mutations can be detected in the plasma using the integrated technique of me-PCR and DHPLC, which enables us to predict patient response to EGFR-TKI therapy. High serum CEA levels served as an independent predictor for plasma EGFR mutations.