title: Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR.
abstract: BACKGROUND
  While epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) lead to longer progression-free survival (PFS) when compared with conventional chemotherapy in non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR-TKI remains unclear in EGFR-wild-type (WT) NSCLC.
  
  
  METHODS
  This article reviews selected data from randomized trials regarding the use of TKIs in EGFR-WT NSCLC. Nine randomized phase III trials have compared EGFR-TKI with chemotherapy in NSCLC patients in a second or later line setting. Two of these trials, TAILOR and DELTA, which were designed to investigate treatment benefits according to EGFR genotype, demonstrated that docetaxel chemotherapy displayed significantly better in progression-free survival (PFS) when compared with the EGFR-TKI erlotinib. Biomarkers to predict clinical benefits of the drug against EGFR WT tumor, and the efficacy of combination regimens using erlotinib or single-use afatinib against tumors are also covered in this article.
  
  
  CONCLUSIONS
  Considering the modest benefits of erlotinib for EGFR-WT tumors, future studies are warranted, including the exploration of useful biomarkers and new treatment strategies for EGFT-TKI use, as well as the development of more sensitive EGFR mutation tests.
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mitsuoka
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: b Department of Respiratory Medicine , Aichi Medical University School of Medicine , Aichi , Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Kubo
authors.affiliation: c Clinical Research Center , National Hospital Organization Kinki-chuo Chest Medical Center , Osaka , Japan.
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Isa
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Asai
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Uji
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sawa
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimoto
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Oka
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakai
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suzumura
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Kuniomi
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kimura
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Naruo
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: a Department of Respiratory Medicine, Graduate School of Medicine , Osaka City University , Osaka , Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Chemotherapy; EGFR tyrosine kinase inhibitor; EGFR wild-type; non-small cell lung cancer; review