title: Correlations of survival with progression-free survival, response rate, and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy.
abstract: BACKGROUND
  The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS).
  
  
  METHODS
  We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated.
  
  
  RESULTS
  Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r(2)=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r(2)-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents.
  
  
  CONCLUSIONS
  The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development.
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Moriwaki
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Faculty of Medicine, Department of Clinical Trial and Clinical Epidemiology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Gosho
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Sugaya
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Endo
authors.affiliation: Faculty of Medicine, Division of Gastroenterology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine