REVIEW
Developmental Therapeutics Consortium report on study design effects on trial outcomes in chronic myeloid leukaemia
Francis Giles,
François-Xavier Mahon,
Bjorn Gjertsen,
Ronan Swords,
Boris Labar,
Anna Turkina,
Gianantonio Rosti,
Francis Giles
HRB Clinical Research Facility, National University of Ireland Galway and Trinity College Dublin, Dublin, Ireland
Search for more papers by this authorFrançois-Xavier Mahon
Université Bordeaux Ségalen, INSERM U1035, Institut Bergonié, Centre Hospitalier universitaire, Bordeaux, France
Search for more papers by this authorBjorn Gjertsen
Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorRonan Swords
Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorBoris Labar
Clinical Hospital Center and School of Medicine, University of Zagreb, Zagreb, Croatia
Search for more papers by this authorAnna Turkina
Hematology Research Center, Moscow, Russian Federation
Search for more papers by this authorGianantonio Rosti
Department of Hematology and Oncology ‘Seragnoli’, Bologna University Hospital, Bologna, Italy
Search for more papers by this authorFrancis Giles,
François-Xavier Mahon,
Bjorn Gjertsen,
Ronan Swords,
Boris Labar,
Anna Turkina,
Gianantonio Rosti,
Francis Giles
HRB Clinical Research Facility, National University of Ireland Galway and Trinity College Dublin, Dublin, Ireland
Search for more papers by this authorFrançois-Xavier Mahon
Université Bordeaux Ségalen, INSERM U1035, Institut Bergonié, Centre Hospitalier universitaire, Bordeaux, France
Search for more papers by this authorBjorn Gjertsen
Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorRonan Swords
Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
Search for more papers by this authorBoris Labar
Clinical Hospital Center and School of Medicine, University of Zagreb, Zagreb, Croatia
Search for more papers by this authorAnna Turkina
Hematology Research Center, Moscow, Russian Federation
Search for more papers by this authorGianantonio Rosti
Department of Hematology and Oncology ‘Seragnoli’, Bologna University Hospital, Bologna, Italy
Search for more papers by this authorFrancis Giles, MD, HRB Clinical Research Facility, University Road, Galway, Ireland. Tel.: Office +353 (91) 495964; fax: +353 (91) 526027; e-mail [email protected]
Abstract
Eur J Clin Invest 2012; 42 (9): 1016–1026
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.
Design 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.
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