Analysis of EGFR mutation status in tissue and plasma for predicting response to EGFR-TKIs in advanced non-small-cell...

The detection of mutations in the epidermal growth factor receptor (EGFR) gene in tumor tissues has been established as the gold standard for predicting the efficacy of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer (NSCLC). The current study aimed to investigate whether the presence of co-existing EGFR mutations in tumor tissue and in cell-free tumor DNA (ctDNA) in the plasma predicts a more favorable outcome of EGFR-TKI treatment in advanced NSCLC. A total of 287 NSCLC patients who had undergone EGFR-TKI treatment were enrolled and stratified into four subgroups: Wild-type EGFR in plasma and tissue specimens (B-/T-); mutated EGFR in plasma and tissue specimens (B+/T+); mutated EGFR in only in plasma samples (B+/T-); or mutated EGFR in only tissue specimens (B-/T+). EGFR mutations were tested using denaturing high-performance liquid chromatography and confirmed by amplification-refractory mutation system analysis. Of the 287 patients, 101 had mutations in both tissue and plasma samples and 103 had mutation in either tissue (n=65) or plasma (n=38). The median progression-free survival (mPFS) times were 9.2 and 2.0 months in the B+/T+ and B-/T- groups, respectively. The mPFS times were 7.9 months in the B-/T+ group and 11.9 months in the B+/T-group (P=0.001). Among the 187 patients with available pre-EGFR-TKI plasma samples, 70 received first-line EGFR-TKI treatment, and the mPFS in the B+/T+ group was longer than in the B-/T+ or B+/T- groups (18.8 vs. 9.4 vs. 6.9 months; P=0.003). In second-line setting of EGFR-TKI therapy, the groups of patients with EGFR mutation in ctDNA, regardless of the mutation status in the tissues, exhibited longer mPFS times compared with the B-/T+ group (10.0 vs. 5.8 months; P=0.044). The results suggest that co-existence of EGFR mutations in tissue and ctDNA predict longer PFS times for NSCLC patients who receive first-line EGFR-TKI therapy. In addition, real-time detection in ctDNA is an excellent predictor for the efficacy of second- or higher line EGFR-TKI therapy.