title: Developmental Therapeutics Consortium report on study design effects on trial outcomes in chronic myeloid leukaemia.
abstract: BACKGROUND
  Tyrosine kinase inhibitors (TKIs) have dramatically changed the treatment of chronic myeloid leukaemia (CML). Results from ongoing phase 3 trials with nilotinib [Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd)] and dasatinib [Dasatinib Versus Imatinib Study in Treatment-Naive CML-CP Patients (DASISION)] in newly diagnosed patients with CML in chronic phase have demonstrated that these TKIs resulted in significant improvements in responses vs. imatinib.
  
  
  METHODS
  The Developmental Therapeutics Consortium (DTC) systematically reviewed the published literature to provide a comparative analysis of the ENESTnd and DASISION trial designs and data reported on each study.
  
  
  RESULTS
  The recent approval of nilotinib and dasatinib based on these two pivotal studies offers physicians the option to optimise frontline treatment based on a patient's comorbidities, risk factors and tolerability profiles. Although nilotinib and dasatinib provide effective therapeutic options for the frontline treatment of CML, the lack of an evidenced-based, side-by-side comparison makes it difficult to directly compare these agents.
  
  
  CONCLUSIONS
  Despite potential bias from differences in patient populations and study design, indirect cross-trial comparisons to determine the relative effectiveness of these agents will be performed by physicians. This DTC report provides a comprehensive summary of the study designs, protocols and results of the ENESTnd and DASISION trials, which will assist physicians in making informed decisions on the best treatment approach for their patients.
authors.affiliation: HRB Clinical Research Facility, National University of Ireland Galway and Trinity College Dublin, Dublin, Ireland. frankgiles@aol.com
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Bjorn
authors.initials: B
authors.lastname: Gjertsen
authors.forename: Ronan
authors.initials: R
authors.lastname: Swords
authors.forename: Boris
authors.initials: B
authors.lastname: Labar
authors.forename: Anna
authors.initials: A
authors.lastname: Turkina
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
mesh_terms: D001549:Benzamides; D002986:Clinical Trials as Topic; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000145:classification / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D012107:Research Design; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib