title: Is response rate increment obtained by molecular targeted agents related to survival benefit in the phase III trials of advanced cancer?
abstract: BACKGROUND
  It remains unclear whether response rate (RR) is related to survival benefit in phase III trials of advanced cancer treated with molecular targeted agents (MTA) in combination with standard therapies.
  
  
  METHODS
  We carried out a systematic search of PubMed for randomized phase III trials of four solid tumors examining the efficacy of MTA when added to a standard therapy. We examined whether there were any associations between RR increment obtained by the addition of targeted agents (DeltaRR) and survival benefit in phase III trials.
  
  
  RESULTS
  We identified 26 phase III trials of MTA with a total of 21 156 patients and 29 experimental arms of MTA. Studies which showed significant survival benefit had higher DeltaRR compared with those which did not show significant benefit. In the receiver operating characteristic curve analysis, using a 7% gain as threshold value for DeltaRR allowed assessment of survival benefit with high sensitivity and specificity. There were also significant relationships between DeltaRR and hazard ratios for overall survival and progression-free survival in the linear regression analysis.
  
  
  CONCLUSIONS
  RR increment obtained by the addition of MTA to a standard therapy may be useful to predict survival benefit in clinical phase III trials of advanced cancer.
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka. Electronic address: ktujino@imed3.med.osaka-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Tsujino
authors.affiliation: Department of Medical Physics, School of Health Sciences, Kumamoto University, Kumamoto.
authors.forename: J
authors.initials: J
authors.lastname: Shiraishi
authors.affiliation: Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Osaka.
authors.forename: T
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Medical Oncology, Kinki University School of Medicine, Osakasayama, Osaka.
authors.forename: T
authors.initials: T
authors.lastname: Kurata
authors.affiliation: Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai, Osaka.
authors.forename: T
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi.
authors.forename: A
authors.initials: A
authors.lastname: Kubo
authors.affiliation: Department of Medical Oncology, Sakai Hospital, Kinki University School of Medicine, Sakai, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takada
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents