The US Food and Drug Administration (FDA) has approved dasatinib (Sprycel, Bristol-Myers Squibb) 100 mg once daily for the treatment of adult patients with newly diagnosed Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
The approval was based on results from the Dasatinib versus Imatinib Study in Treatment-Naïve CP-CML Patients (DASISION) open-label, phase 3 trial, which were published in the New England Journal of Medicine and presented at the 2010 annual meeting of the American Society of Clinical Oncology in June 2010 by Hagop M. Kantarjian, MD, of The University of Texas MD Anderson Cancer Center, Houston. The trial is ongoing and further data will be required to determine long-term outcome.
In the international trial, dasatinib 100 mg taken once daily was compared with imatinib 400 mg taken once daily, in the treatment of newly diagnosed chronic-phase Ph+ CML.Of the 519 patients enrolled in the study, 259 received dasatinib and 260 received imatinib.
Compared with imatinib, dasatinib demonstrated superior efficacy with higher and faster molecular and confirmed cytogenetic response rates in newly diagnosed CP-CML patients. Confirmed cytogenic response (CCyR), the primary end point, was achieved by 12 months in 77% of dasatinib patients versus 66% of those who received imatinib.Median time to confirmed CCyR was 3.1 months in 199 dasatinib responders and 5.6 months in 177 imatinib responders. Median time to major molecular response (MMR) was 6.3 months in dasatinib responders and 9.2 months in imatinib responders. MMR at anytime was higher for dasatinib patients versus imatinib. Transformation to accelerated or blast phase occurred in five dasatinib patients and nine imatinib patients.
The most frequently reported serious adverse reactions included pleural effusion (2%), hemorrhage (2%), congestive heart failure (1%), and pyrexia (1%). The most frequently reported adverse reactions reported in ≥10% of dasatinib patients included myelosuppression, fluid retention events, diarrhea, headache, musculoskeletal pain, and rash.
Dasatinib initially received accelerated FDA approval in June 2006 as a treatment for adults for all phases of Ph+ CML with resistance or intolerance to prior therapy including imatinib. Full approval was granted in May 2009.
Imatinib (Gleevec, Novartis) was the first targeted therapy approved for the treatment of Ph+ CML Ph+ CML. Last June, nilotinib (Tasigna, Novartis) was granted approval for that indication.