title: Impact of Geographic Region on Benefit of Approved Anticancer Drugs Evaluated in International Phase III Clinical Trials.
abstract: OBJECTIVE
  International collaboration allows for enhanced accrual and more generalisable results of phase III randomised controlled trials (RCTs). The impact of geographic region on the outcomes of new anticancer agents is unclear.
  
  
  METHODS
  International RCTs evaluating approved systemic therapy for advanced solid tumours that reported efficacy of new anticancer drugs based on geographic regions were eligible. Data for overall (OS) or progression-free survival (PFS) were pooled in a meta-analysis. The primary analysis was the comparison of developed versus developing countries. A meta-regression analysis explored the impact of differences in gross national income (GNI) per capita on the hazard ratio comparing developed and developing countries. Secondary analyses compared geographic regions irrespective of GNI.
  
  
  RESULTS
  Of the 63 identified studies, 12 independent RCTs were eligible; five reported data for OS and nine for PFS. Improvements in overall survival were greater in developed as compared with developing countries (hazard ratio 0.82, 95% confidence interval 0.68-0.99, P = 0.04). This effect was seen only among studies of cytotoxic chemotherapy and not among those of targeted agents. No difference was seen for PFS (hazard ratio 0.93, 95% confidence interval 0.79-1.09, P = 0.36). Meta-regression showed a significant negative association between GNI per capita and overall survival, but a non-significant negative association with PFS (β = -0.774, P = 0.05 and β = -0.211, P = 0.29, respectively). No differences were observed in PFS between Asian and non-Asian countries or North America and Western Europe.
  
  
  CONCLUSIONS
  Compared with patients from developing countries, those from developed countries derive greater improvement in overall survival from cytotoxic chemotherapy, but similar benefit from targeted drugs.
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, King Saud Medical City, Riyadh, Saudi Arabia.
authors.forename: H Y
authors.initials: HY
authors.lastname: AlHashem
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Al-Mubarak
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: F E
authors.initials: FE
authors.lastname: Vera-Badillo
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Translational Research Unit, Albacete University Hospital, Calle Laurel, Albacete, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ocana
authors.affiliation: Sector of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: B
authors.initials: B
authors.lastname: Seruga
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: eitan.amir@uhn.ca.
authors.forename: E
authors.initials: E
authors.lastname: Amir
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D019049:Developed Countries; D005843:Geography; D006801:Humans; D007390:International Agencies; D015201:Meta-Analysis as Topic; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents
keywords: Developed countries; developing countries; disparity; randomised trials; survival