title: What is an active regimen in carcinoma of unknown primary sites? Analysis of correlation between activity endpoints reported in phase II trials. Correlation of activity endpoints in phase II trials.
abstract: BACKGROUND
  The choice of the activity endpoint is crucial when designing phase II screening trials. This choice is usually guided by convention, but the level of evidence for picking-up one of them is limited.
  
  
  METHODS
  We have analysed the phase II trials in carcinoma of unknown primary patients (CUP; 48 strata). We calculated the Pearson correlation coefficient using weighted linear regression to measure the degree of association between the different available activity endpoints (Best objective response - BORR, best tumour control rate - BTCR, 3- and 6-month progression-free rates, 3- and 6-month PFR and median progression-free survival). We also explored the correlation between these endpoints and OS.
  
  
  RESULTS
  All activity endpoints were strongly correlated in CUP studies; all of these endpoints were strongly correlated with OS. The median BORR across the studies was 30%. Positive trials defined by BORR ≥ 30% were associated with statistically longer PFS (4.8 versus 3.7 months, P = 0.013) and OS (10.0 versus 8.0, P = 0.0007).
  
  
  CONCLUSIONS
  In phase II studies with CUP patients, BORR and the threshold of BORR > 30% for defining promising drug appears adequate.
authors.affiliation: Centre Oscar-Lambret, General Oncology Department, 3, rue Frédéric-Combemale, 59020 Lille cedex, France, Lille Nord-de-France University, Unit Research (EA 2694) Medical School, 1, place de verdun, 59000 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Penel
authors.affiliation: Centre Oscar-Lambret, General Oncology Department, 3, rue Frédéric-Combemale, 59020 Lille cedex, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryckewaert
authors.affiliation: Lille Nord-de-France University, Unit Research (EA 2694) Medical School, 1, place de verdun, 59000 Lille, France, Centre Oscar-Lambret, Methodology and Biostatistics Unit, 3, rue Frédéric-Combemale, 59020 Lille cedex, France.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kramar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D006801:Humans; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: activity endpoint; advanced soft-tissue sarcoma; carcinoma of unknown primary; correlation; phase II trials