Estimation of cell-free circulating EGFR mutation concentration predicts outcomes in NSCLC patients treated with EGFR-TKIs

• DOI: 10.18632/oncotarget.14490
• Publication Date: 2017-01-07T00:30:52Z
• Authors: Yan-juan Zhu; Hai-bo Zhang; Yi-hong Liu; Fu-li Zhang; Ya-zhen Zhu; Yong Li; Jian-ping Bai; Li-rong Liu; Yan-chun Qu; Xin Qu; Xian Chen; Yan Li; Guang-juan Zheng
• Keywords: Male; Lung Neoplasms; droplet digital polymerase chain reaction; Clinical Sciences; Oncology and Carcinogenesis; 610; Kaplan-Meier Estimate; Disease-Free Survival; Erlotinib Hydrochloride; 03 medical and health sciences; 0302 clinical medicine; Clinical Research; Carcinoma, Non-Small-Cell Lung; Humans; Non-Small-Cell Lung; Lung; Protein Kinase Inhibitors; non-small cell lung cancer; Cancer; Aged; Biomedical and Clinical Sciences; Lung Cancer; Carcinoma; Evaluation of treatments and therapeutic interventions; Oncology and carcinogenesis; Gefitinib; Middle Aged; Prognosis; 3. Good health; ErbB Receptors; Treatment Outcome; 6.1 Pharmaceuticals; Mutation; Quinazolines; Female; blood biopsy; epidermal growth factor receptor; Research Paper

Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8.43 months) than low baseline pEGFRmut (16.23 months; p = 0.0019). By contrast, there were no differences in tumor shrinkage or overall survival between groups. During EGFR-TKI treatment, pEGFRmut levels decreased to zero in 89.58% of patients. Twenty-five of the 27 patients who progressed had basal pEGFRmut, and 18 also had circulating T790M. All 20 patients with dramatic progression (according to a categorization system for EGFR-TKIs failure) had basal pEGFRmut, and 13 had T790M mutation at progression. These results support the use of ddPCR for analysis of plasma EGFR mutations for prediction of PFS and to monitor clinical responses to EGFR-TKIs in NSCLC patients.