title: Patients harboring epidermal growth factor receptor (EGFR) double mutations had a lower objective response rate than those with a single mutation in non-small cell lung cancer when treated with EGFR-tyrosine kinase inhibitors.
abstract: BACKGROUND
  Multiple prospective studies have demonstrated that epidermal growth factor receptor (EGFR) exon 19 and exon 21 mutations are the most powerful predictive biomarkers of response to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). However, there are few studies focused on patients with double mutations compared with a single mutation.
  
  
  METHODS
  We retrospectively screened 1,525 samples of Chinese patients with advanced NSCLC who underwent EGFR mutation detections in tumor tissues at Peking University Cancer Hospital between February 2006 and March 2011. Thirty-two cases harboring double mutations were included in this study. The Kaplan-Meier univariate analysis for prognostic factors of survival was applied.
  
  
  RESULTS
  Patients with double mutations accounted for 2.1% (32/1525) of the overall tested samples. Double mutations were more common in female, adenocarcinoma, non-smokers, Eastern Cooperative Oncology Group (ECOG0)-1 and stage IV patients. Twenty-one patients with double mutations were treated with EGFR-TKIs. The objective response rate (ORR) was 23.8%, and the disease control rate (DCR) was 76.2%. In the first-line therapy, the ORR was 16.7%, and the DCR was 66.7%. In univariate analysis, gender, smoking-status, TKI type and TKI response were correlated with progression-free survival, and patients with ECOG 0-1 had longer overall survival.
  
  
  CONCLUSIONS
  Patients with double mutations had a low objective response rate when treated with EGFR-TKIs compared with single EGFR exon 19 or exon 21 mutations.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: An
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Keneng
authors.initials: K
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Duan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Meina
authors.initials: M
authors.lastname: Wu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Minglei
authors.initials: M
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Xuyi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
keywords: DHPLC; double mutations; epidermal growth factor receptor; lung neoplasms; tyrosine kinase inhibitor