The content of mutant EGFR DNA correlates with response to EGFR-TKIs in lung adenocarcinoma patients with common EGFR mutations

Abstract

This study aimed to elucidate the association of the content of mutant epidermal growth factor receptor (EGFR) deoxyribonucleic acid (DNA) with the treatment response to EGFR-tyrosine kinase inhibitor (TKI) and survival in patients with lung cancer.This retrospective cohort study included 77 lung adenocarcinoma patients with common EGFR mutations from December 2012 to February 2015. The content of mutant EGFR DNA in lung cancer tissues was determined using an Amplification Refractory Mutation System. The association of the amount of mutant EGFR DNA with treatment response, the clinical variables, and the progression-free survival (PFS) after EGFR-TKI therapy were evaluated.Using the amount of mutant EGR DNA above 4.77% as the cut-off value, the sensitivity to predict EGFR-TKI responder is 82.0% and the specificity is 75.0% (area under the curve [AUC]: 0.734, P = 0.003). The high content of mutant EGFR DNA is an independent factor associated with the response to EGFR-TKIs (odds ratio: 13.07, 95% confidence interval [CI]: 3.23-52.11, P = 0.0003). A significantly longer PFS was observed in the group with the high content of mutant EGFR DNA (26.3 months, 95% CI: 12.2-26.3) compared with the low content of mutant EGFR DNA groups (12.3 months, 95% CI: 5.7-14.8, P = 0.0155). A better predictive value of the content of mutant EGFR DNA was noted in patients with exon 19 deletions (AUC: 0.892, P < 0.0001) than exon 21 L858R mutations (AUC: 0.675, P = 0.0856).Our results show that the content of mutant EGFR DNA is associated with the clinical response to EGFR-TKIs, especially in patients with exon 19 deletions mutation.

Figure 1

The association of the percentage of EGFR mutant DNA and delta Ct determined by the Therascreen EGFR RGQ PCR kit (Qiagen) in lung cancer cells. DNA = deoxyribonucleic acid, EGFR = epidermal growth factor.

Figure 2

(A) ROC curve of using the amount of mutant EGFR DNA to predict EGFR-TKI responder in lung adenocarcinoma patients with exon 19 deletions and exon 21 L858R mutations. (B) PFS of the patients with high and low content of mutant EGFR DNA after EGFR-TKI therapy. DNA = deoxyribonucleic acid, EGFR-TKI = epidermal growth factor tyrosine kinase inhibitor, PFS = progression-free survival, ROC = receiver operating characteristic.

Figure 3

ROC curve of using the amount of mutant EGFR DNA to predict EGFR-TKI responder in lung adenocarcinoma patients with (A) exon 19 deletions and (B) exon 21 L858R mutations. DNA = deoxyribonucleic acid, EGFR-TKI = epidermal growth factor tyrosine kinase inhibitor, ROC = receiver operating characteristic.

Figure 4

PFS of the patients with high and low content of mutant EGFR DNA after EGFR-TKI therapy in lung adenocarcinoma patients with (A) exon 19 deletions and (B) exon 21 L858R mutations. DNA = deoxyribonucleic acid, EGFR-TKI = epidermal growth factor tyrosine kinase inhibitor, PFS = progression-free survival.