title: Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?
abstract: OBJECTIVE
  To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors.
  
  
  METHODS
  We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models.
  
  
  RESULTS
  Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial.
  
  
  CONCLUSIONS
  In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143-1702, USA. chanjohn@obgyn.ucsf.edu
authors.forename: John K
authors.initials: JK
authors.lastname: Chan
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Ueda
authors.forename: Valerie E
authors.initials: VE
authors.lastname: Sugiyama
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Stave
authors.forename: Jacob Y
authors.initials: JY
authors.lastname: Shin
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Branimir I
authors.initials: BI
authors.lastname: Sikic
authors.forename: Kathryn
authors.initials: K
authors.lastname: Osann
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kapp
mesh_terms: D000047:Academies and Institutes; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004345:Drug Industry; D006801:Humans; D018156:Journalism, Medical; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012107:Research Design; D012189:Retrospective Studies; D013997:Time Factors; D014495:Universities
chemical_list: D000970:Antineoplastic Agents