title: T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients.
abstract: OBJECTIVE
  Continuous EGFR-TKI treatment beyond progression has shown promising benefit for some patients with acquired resistance to EGFR-TKIs. The aim of this study was to investigate the association of secondary T790M mutation at the time of progression with the efficacy of EGFR-TKI treatment beyond progression.
  
  
  METHODS
  From March 2011 to March 2013, patients with advanced NSCLC who developed acquired resistance to EGFR-TKI and where a re-biopsy was performed at Tongji University Cancer Institute were included into this study. Scorpion ARMS was used to detect EGFR mutation status.
  
  
  RESULTS
  A total of 54 patients were enrolled in this study with a median progression-free survival time (PFS1) of 10.9 months according to RECIST criteria. In all, 53.7% (29/54) had T790M mutation after the failure of EGFR-TKIs; PFS1 was not statistically significantly different between patients with T790M mutation and without (13.0 vs. 10.5 months, p = 0.894). In all, 41 patients received TKI treatment beyond progression, including 22 with local progression to receive additional local therapy and 19 with gradual progression to receive additional chemotherapy. The median progression-free survival time (PFS2) of patients who received EGFR-TKI beyond progression treatment was 3.5 months (95% CI, 2.689-4.311). Patients with T790M mutation had significantly longer PFS2 (6.3 vs. 2.6 months, p = 0.002) and overall survival (39.8 vs. 23.2 months, p = 0.044) than those without.
  
  
  CONCLUSIONS
  Patients with secondary T790M mutation at the time of progression having gradual or local progression after acquired resistance to EGFR-TKI benefit more from EGFR-TKI treatment beyond progression compared to those without T790M mutation.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Aiwu
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Cao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Yayi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Imaging, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, PR China. Electronic address: caicunzhoudr@163.com.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, Shanghhai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Fei
authors.affiliation: Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of Heidelberg University, Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmid-Bindert
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D043844:Crown Ethers / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D043844:Crown Ethers; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C531470:icotinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Acquired assistance; EGFR-TKI; NSCLC; Secondary T790M mutation