title: Activity endpoints reported in soft tissue sarcoma phase II trials: quality of reported endpoints and correlation with overall survival.
abstract: BACKGROUND
  Despite extensive research over the past 3 decades, few investigational drugs are considered as promising and these drugs failed to improve overall survival. Therefore we performed a systematic review of the literature to improve our understanding of the reasons that explain these failures.
  
  
  METHODS
  We reviewed 53 phase II trial reports that investigated new treatments in patients with advanced soft tissue sarcoma from 1999 to 2011. We critically reviewed the selected primary endpoint used in these trials.
  
  
  RESULTS
  Forty percent of trials were not interpretable because of major inherent methodological flaws. Only 3 primary endpoints were correlated with median overall survival (mOS): 3- and 6-month progression free rates and median progression-free survival. Nevertheless, the mOS was not significantly higher in the cases of active drugs.
  
  
  CONCLUSIONS
  We need to improve the definition of primary active endpoints and develop better designs for future trials. The current definition of promising drugs must be refined.
authors.affiliation: General Oncology Department, Centre Oscar Lambret, Lille, France; Unit Research (EA 2694), Medical School, Lille-Nord-de-France University, Lille, France. Electronic address: n-penel@o-lambret.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.forename: Sophie
authors.initials: S
authors.lastname: Cousin
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: 3-month progression free rate; 6-month progression free rate; Activity endpoint; Advanced soft tissue sarcoma; BORR; BTCR; Correlation; EORTC; European Organization on Research and Treatment of Cancer; PFR3; PFR6; Phase II trials; best objective response rate; best tumor control rate; mOS; mPFS; median overall survival; median progression free survival