title: Response rate is associated with prolonged survival in patients with advanced non-small cell lung cancer treated with gefitinib or erlotinib.
abstract: BACKGROUND
  Gaining a higher response rate (RR) has usually been determined as a primary end point in phase II trials evaluating the efficacy of new molecular targeted drugs. However, a relationship between clinical response and survival benefit has not been well studied in the patients treated with molecular targeted agents.
  
  
  METHODS
  Prospective trials of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) monotherapy in non-small cell lung cancer were extracted from MEDLINE, EMBASE, and the annual meetings in 2007 of the American Society of Clinical Oncology, European Cancer Conference, and World Conference on Lung Cancer. Correlation between clinical response and survival was examined using linear regression analysis. We also tried to compare the significance of RR as surrogate markers for survival with that of disease control rate (DCR) by calculating the area under their receiver operating characteristic (ROC) curves.
  
  
  RESULTS
  We identified 24 phase II trials and 4 phase III trials with a total of 6171 patients and 30 treatment arms, including 22 arms for the gefitinib group and 8 arms for the erlotinib group. Both RR and DCR strongly correlated with median survival time (MST; p < 0.0001 and p = 0.003, respectively). In an ROC analysis, the area under the ROC curve predicting MST prolongation by RR was 0.918, which was higher than the area under the ROC curve by DCR.
  
  
  CONCLUSIONS
  We found a significant relationship between RR and MST in clinical trials with EGFR-TKIs. RR could be an independent surrogate marker for MST in the current response criteria in the clinical trials of EGFR-TKIs.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsujino
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Akihito
authors.initials: A
authors.lastname: Kubo
authors.forename: Nana
authors.initials: N
authors.lastname: Aono
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakao
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Koh
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Tachibana
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Isa
authors.forename: Minoru
authors.initials: M
authors.lastname: Takada
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kurata
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D016208:Databases, Factual; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D012372:ROC Curve; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib