title: Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials.
abstract: BACKGROUND
  Two recent studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). This pre-planned analysis evaluates the efficacy of CisGem with increased statistical power.
  
  
  METHODS
  We carried out a meta-analysis of individual patient-level data of these studies to establish the effect of CisGem versus Gem on progression-free survival (PFS), overall survival (OS) and carried out exploratory subgroup analyses.
  
  
  RESULTS
  CisGem demonstrates a significant improvement in PFS [hazard ratio (HR)=0.64, 95% confidence interval (CI) 0.53-0.76, P<0.001] and OS (HR=0.65, 95% CI 0.54-0.78, P<0.001) over Gem. This effect is most marked among patients with good performance status (PS 0-1): HR for PFS is 0.61 (95% CI 0.51-0.74), P<0.001 and OS HR=0.64 (95% CI 0.53-0.77), P<0.001. CisGem resulted in improved PFS and OS for intra- and extra-hepatic cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and Japanese patients was consistent with respect to OS (HR=0.65, 95% CI 0.53-0.79 and 0.65, 95% CI 0.42-1.03, respectively); with similar OS in the combination arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to benefit included patients with ampullary tumours and poor performance status (PS2).
  
  
  CONCLUSIONS
  CisGem is the standard of care for the first-line treatment of good-PS patients with advanced BTC regardless of ethnicity. Future studies should aim to enhance the effectiveness of this regimen in the first-line setting, establish the role of subsequent (second-line) therapy and assess the role of rationally developed molecular-targeted therapies.
authors.affiliation: Manchester Academic Health Sciences Centre, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Valle
authors.forename: J
authors.initials: J
authors.lastname: Furuse
authors.forename: M
authors.initials: M
authors.lastname: Jitlal
authors.forename: S
authors.initials: S
authors.lastname: Beare
authors.forename: N
authors.initials: N
authors.lastname: Mizuno
authors.forename: H
authors.initials: H
authors.lastname: Wasan
authors.forename: J
authors.initials: J
authors.lastname: Bridgewater
authors.forename: T
authors.initials: T
authors.lastname: Okusaka
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: biliary tract cancer; cholangiocarcinoma; cisplatin; gallbladder cancer; gemcitabine