Dynamic Plasma EGFR Mutation Status as a Predictor of EGFR-TKI Efficacy in Patients with EGFR-Mutant Lung Adenocarcinoma
Authors: Jeng-Sen Tseng, Tsung-Ying Yang, Chi-Ren Tsai, Kun-Chieh Chen, Kuo-Hsuan Hsu, Meen-Hsin Tsai, Sung-Liang Yu, Kang-Yi Su, Jeremy J.W. Chen, Gee-Chen Chang
Journal: Journal of Thoracic Oncology (2014)

BackgroundEpidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction.MethodsAdvanced lung adenocarcinoma patients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid–zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens.ResultsA total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1a patients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6–11.0) and 20.5 months (95% CI 15.1–26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13–24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33–2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04–3.18], p = 0.036).ConclusionChanges in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid–zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor. Epidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction. Advanced lung adenocarcinoma patients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid–zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens. A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1a patients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6–11.0) and 20.5 months (95% CI 15.1–26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13–24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33–2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04–3.18], p = 0.036). Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid–zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.