A Phase III study (the DASISION study), has found that after one year, dasatinib (Sprycel), a highly potent BCR-ABL kinase inhibitor, is superior to the standard first-line drug, imatinib (Gleevec), for bringing about cytogenetic and molecular responses in patients newly diagnosed with chronic myeloid leukemia (CML).The study results from this Phase II study, were presented during the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from June 4 – 8 in Chicago, IIllinois (USA).
?We?ve been seeing more CML patients developing imatinib resistance, so these results are very exciting,? said lead author Hagop Kantarjian, MD, professor and chair of the leukemia department at the University of Texas M. D. Anderson Cancer Center in Houston. ?Our findings suggest that by using dasatinib upfront in patients newly diagnosed with CML, we can improve outcomes.?
Approximately one-third of patients newly diagnosed with CML fail to achieve a complete cytogenetic response (CCyR) by 12 months with imatinib, developing resistance to the drug and increasing the risk of disease progression. A CCyR means the complete disappearance of cells with the Philadelphia chromosome, the genetic abnormality created by the fusion of two genes, BCR and ABL. The abnormality results in the cancer-causing tyrosine kinase enzyme, BCR-ABL, which acts like a switch stuck in the ?on? position, driving the overproduction of white blood cells and the development of CML. CCyR is known to be a very good surrogate marker for long-term survival for CML patients.
Both imatinib and dasatinib work by targeting BCR-ABL. Dasatinib is currently approved for CML patients whose disease persists despite imatinib or who cannot tolerate imatinib, but it is not approved as initial therapy.
In this study, Dr. Kantarjian and his team compared the CCyR in patients newly diagnosed with CML who were randomly assigned to receive 12 months of dasatinib (259 patients) or imatinib (260 patients). After a year, the rate of confirmed CCyR was significantly higher among patients who received dasatinib (77%) than imatinib (66%). The rate of major molecular responses ? another marker of drug effectiveness ? was also higher with dasatinib (46%) than imatinib (28%). Both drugs were generally well tolerated.
The researchers plan to continue to monitor patients? progress over time ? there is no survival data as yet ? including progression-free and overall survival. Other tyrosine kinase inhibitors are also being tested for early-stage CML patients.
Oral Abstract Session: Leukemia, Myelodysplasia, and Transplantation
Lead Author: Hagop Kantarjian, MD, The University of Texas M. D. Anderson, Houston, Texas
Date:Monday, June 7, 2010, 9:30-9:45 AM CDT
Location: Room E354b
Title:Dasatinib compared to imatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia in chronic phase (CMLCP): 12-month efficacy and safety from the phase 3 DASISION study.
Authors: H. Kantarjian, N. P. Shah, A. Hochhaus, J. E. Cortes, S. Shah, M. Ayala, B. Moiraghi, M. Bradley-Garelik, C. Zhu, M. Baccarani.