title: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment Response in Advanced Lung Adenocarcinomas with G719X/L861Q/S768I Mutations.
abstract: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. Preclinical studies have suggested that uncommon G719X, L861Q, and S768I mutations are also sensitive to EGFR-TKIs. However, the efficacy of EGFR-TKIs in patients with these uncommon mutations remains unclear.
  
  
  
  A nationwide survey was performed to collect data from gefitinib and erlotinib treatment outcomes of patients with stage IIIB/IV lung adenocarcinoma bearing EGFR G719X/L861Q/S768I mutations. The results were compared with those regarding patients with exon 19 deletions or L858R mutations.
  
  
  
  One hundred and sixty-one patients with uncommon EGFR mutations were enrolled from 18 institutes throughout Taiwan. Mutations of G719X, L861Q, S768I, G719X + L861Q, and G719X + S768I were observed in 78, 57, 7, 9, and 10 patients, respectively. After receiving EGFR-TKI treatment, patients with uncommon mutations exhibited a significantly inferior tumor response rate (41.6% vs. 66.5%; p < 0.001) and progression-free survival (median, 7.7 vs. 11.4 months; p < 0.001) than patients with common mutations. Among the patients who used EGFR-TKIs as first-line treatment, there was a significant difference in overall survival between these two groups of patients (median, 24.0 vs. 29.7 months; p = 0.005).
  
  
  
  Gefitinib and erlotinib are active in patients with G719X/L861Q/S768I mutations; however, less effective than in those with common mutations.
authors: Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. Electronic address: jhchiou@vghtpe.gov.tw.
authors: Chao-Hua
authors: CH
authors: Chiu
authors: Department of Thoracic Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors: Cheng-Ta
authors: CT
authors: Yang
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan.
authors: Jin-Yuan
authors: JY
authors: Shih
authors: Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Ming-Shyan
authors: MS
authors: Huang
authors: Department of Internal Medicine, National Cheng Kung University Hospital and National Cheng Kung University, Tainan, Taiwan.
authors: Wu-Chou
authors: WC
authors: Su
authors: Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors: Ruay-Sheng
authors: RS
authors: Lai
authors: Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors: Chin-Chou
authors: CC
authors: Wang
authors: Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors: Shih-Hsin
authors: SH
authors: Hsiao
authors: Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi and Chang Gung University, Taoyuan, Taiwan.
authors: Yu-Ching
authors: YC
authors: Lin
authors: Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
authors: Ching-Liang
authors: CL
authors: Ho
authors: Department of Respiratory Therapy, China Medical University Hospital and China Medical University, Taichung, Taiwan.
authors: Te-Chun
authors: TC
authors: Hsia
authors: School of Medicine, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan.
authors: Ming-Fang
authors: MF
authors: Wu
authors: Department of Internal Medicine, Buddhist Dalin Tzu Chi Hospital, Chiayi and Tzu Chi University, Hualien, Taiwan.
authors: Chun-Liang
authors: CL
authors: Lai
authors: Department of Pulmonary Medicine, Shuang Ho Hospital and Taipei Medical University, Taipei, Taiwan.
authors: Kang-Yun
authors: KY
authors: Lee
authors: Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors: Chih-Bin
authors: CB
authors: Lin
authors: Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors: Diana
authors: D
authors: Yu-Wung Yeh
authors: Department of Internal Medicine, Ren-ai Branch, Taipei City Hospital, Taipei, Taiwan.
authors: Chi-Yuan
authors: CY
authors: Chuang
authors: Department of Internal Medicine, Zhong-xiao Branch, Taipei City Hospital, Taipei, Taiwan.
authors: Fu-Kang
authors: FK
authors: Chang
authors: Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
authors: Chun-Ming
authors: CM
authors: Tsai
authors: Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.
authors: Reury-Perng
authors: RP
authors: Perng
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan.
authors: James
authors: J
authors: Chih-Hsin Yang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib