title: Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials.
abstract: OBJECTIVE
  Objective tumor response rates observed in phase II trials for metastatic melanoma have historically not provided a reliable indicator of meaningful survival benefits. To facilitate using overall survival (OS) or progression-free survival (PFS) as an endpoint for future phase II trials, we evaluated historical data from cooperative group phase II trials to attempt to develop benchmarks for OS and PFS as reference points for future phase II trials.
  
  
  METHODS
  Individual-level and trial-level data were obtained for patients enrolled onto 42 phase II trials (70 trial arms) that completed accrual in the years 1975 through 2005 and conducted by Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, and the Clinical Trials Group of the National Cancer Institute of Canada. Univariate and multivariate analyses were performed to identify prognostic variables, and between-trial(-arm) variability in 1-year OS rates and 6-month PFS rates were examined.
  
  
  RESULTS
  Statistically significant individual-level and trial-level prognostic factors found in a multivariate survival analysis for OS were performance status, presence of visceral disease, sex, and whether the trial excluded patients with brain metastases. Performance status, sex, and age were statistically significant prognostic factors for PFS. Controlling for these prognostic variables essentially eliminated between-trial variability in 1-year OS rates but not in 6-month PFS rates.
  
  
  CONCLUSIONS
  Benchmarks are provided for 1-year OS or OS curves that make use of the distribution of prognostic factors of the patients in the phase II trial. A similar benchmark for 6-month PFS is provided, but its use is more problematic because of residual between-trial variation in this endpoint.
authors.affiliation: Biometric Research Branch, EPN-8129, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. korne@ctep.nci.nih.gov
authors.forename: Edward L
authors.initials: EL
authors.lastname: Korn
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Liu
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Judith-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Donna
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Eisenhauer
authors.forename: Wendy
authors.initials: W
authors.lastname: Parulekar
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.forename: Scott
authors.initials: S
authors.lastname: Saxman
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
mesh_terms: D019985:Benchmarking; D001932:Brain Neoplasms / Q000556:secondary; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D006801:Humans; D008545:Melanoma / Q000401:mortality* / Q000556:secondary* / Q000628:therapy*; D015201:Meta-Analysis as Topic; D015999:Multivariate Analysis; D011379:Prognosis; D012107:Research Design / Q000706:statistics & numerical data; D018401:Sample Size; D012878:Skin Neoplasms / Q000401:mortality* / Q000628:therapy*; D016019:Survival Analysis; D015996:Survival Rate