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A7088 - Detecting EGFR Mutations from Plasma cfDNA in Lung Adenocarcinoma Patients
Author Block: M. Hung, J. Lung, Y. Lin, Y. Fang, Y. Tsai; Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital Chiayi, Puzi City, Taiwan.
Background: This study aimed to compare two methods for detection of EGFR mutations from cfDNA in lung adenocarcinoma patients. Patients and Methods: Totally, 77 lung adenocarcinoma patients (57 with EGFR mutations and 20 with without EGFR mutations) were enrolled for EGFR mutation analysis in plasma cfDNA and lung cancer tissue from February 2013 to March 2017. Methods using the Therascreen® EGFR RGQ PCR kit (ARMS) and OncoFOCUS™ Panel v1.0 (Sequenom) with the mass-spectroscopy based MassArray device were used to detect EGFR mutations. The clinical prognosis in 43 patients received first-line EGFR-TKI therapy was also evaluated. Results: Using EGFR mutation in lung cancer tissue as the standard, the sensitivity of the ARMS method was 49.1% and the specificity was 90%. The sensitivity of the Sequenom method was 56% and the specificity was 95%. The agreement between ARMS and Sequenom was then evaluated and very good agreement between these two methods was observed (kappa: 0.88, 95% CI: 0.77-0.99). For exon 19 deletions EGFR mutation, the sensitivity and specificity of ARMS and Sequenom methods were 50% vs 53.8% and 95.6% vs 97.7%. For exon 21 L858R EGFR mutation, the sensitivity and specificity of of ARMS and Sequenom methods were 45% vs 47.4% and 100% vs 100%. For exon 20 T790M EGFR mutation, the sensitivity and specificity of of ARMS and Sequenom methods were 33.3% vs 50% and 100% vs 100%. Among those 77 patients studied, 43 patients with common activating EGFR mutations (exon 21 L858R and exon 19 deletions) received first-line EGFR-TKI therapy. All of these patients were stage IIIB or IV lung adenocarcinoma patients. Among those 43 patients, the presence of EGFR mutation in plasma cfDNA after EGFR-TKI treatment was significantly associated with inferior PFS (9.0 months, 95% CI: 7.0-11.8 months vs 15.0 months, 95% CI: 11.7-28.2 months, p=0.02) and OS (30.6 months, 95% CI: 12.4-37.2 months vs 55.6 months, 95% CI: 25.8- 61.8 months, p=0.03) compared to those without detectable EGFR mutation. Conclusions: Our work adds another evidence that detection of EGFR mutation in cfDNA in plasma appears to be a promising and minimally invasive alternative to tumor biopsy for patients without available tissue samples. Patients with common EGFR mutations detected in the blood have worse prognosis compared with blood EGFR mutation-negative patients after first-line EGFR-TKI therapy.