title: Detection of epidermal growth factor receptor mutations in plasma by mutant-enriched PCR assay for prediction of the response to gefitinib in patients with non-small-cell lung cancer.
abstract: The high frequency of epidermal growth factor receptor (EGFR) mutations in tyrosine kinase inhibitor-responsive non-small-cell lung cancer (NSCLC) cases is now well established, highlighting the predictive value of activating EGFR mutations in guiding the clinical use of EGFR-targeted therapies. However, specimen source and methods for EGFR mutation analysis are limited by tissue availability and technical feasibility in clinical application. Therefore, the current study is designed to establish a blood-based approach for the assessment of EGFR mutations in NSCLC patients, in particular the advanced stage, and to test its clinical application. Plasma samples were obtained from the enrolled 134 NSCLC patients. The detection rate of the EGFR exon19 deletions and exon21 L858R was 49.3% (66/134) by the blood-based, mutant-enriched polymerase chain reaction. In the paired tumor and plasma samples, the detected mutant types of each pair respectively by direct sequencing and mutant-enriched polymerase chain reaction were concordant in 17 of 18 (94.4%). In the patients treated with gefitinib as a second-line therapy, those with plasma EGFR mutation have a prolonged median progression-free survival compared with those with EGFR wild type (7.609 vs. 2.877 months, p = 0.002). On comparing the efficacy of gefitinib with that of docetaxel, it was found that the median progression-free survival was significantly longer for patients treated with gefitinib than those with docetaxel in those harboring plasma EGFR mutation (7.609 vs. 3.192 months, p = 0.006). These results suggest that the blood-based EGFR mutations test has the ability to provide a reliable guidance for clinical decision making for the treatment of the advanced NSCLC patients.
authors.affiliation: State Key Lab of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou Medical College, Guangzhou 510120, China.
authors.forename: Chen
authors.initials: C
authors.lastname: He
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Zhou
authors.forename: Jiexia
authors.initials: J
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Ouyang
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000097:blood* / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib