FDA Grants Accelerated Approval to Dasatinib
Thursday, October 28, 2010
The U.S. Food and Drug Administration granted accelerated approval to dasatinib [Sprycel®, Bristol-Myers Squibb], an orally administered kinase inhibitor, for the treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (CP-CML). The recommended dasatinib dose for this indication is 100 mg orally once daily. Sprycel was originally approved in June 2006 for the treatment of adult patients with CP-CML resistant or intolerant to prior therapy that included imatinib.
The efficacy and safety of dasatinib in adults with newly diagnosed CP-CML were demonstrated in a single randomized, active-control, open-label multinational clinical trial. Five hundred and nineteen patients were randomized to receiver either dasatinib 100 mg QD (n = 259) or imatinib 400 mg QD (n = 260). The primary objective was to compare the rate of confirmed complete cytogenetic response (CCyR) by 12 months between the two treatment arms. Confirmed CCyR was defined as a CCyR noted on two consecutive occasions at least 28 days apart. The rate of major molecular response (MMR) at any time was a secondary endpoint. MMR was defined as BCR-ABL ratios ≤ 0.1% by RQ-PCR in peripheral blood samples standardized on the International scale.
The primary efficacy endpoint, rate of confirmed CCyR by 12 months, was achieved in 199 patients (76.8%) and in 172 patients (66.2%) on the dasatinib and imatinib arms, respectively ( p= 0.007). The rate of MMR at any time was also higher in the dasatinib arm compared to the imatinib arm: 52.1% versus 33.8% in the dasatinib and imatinib groups, respectively (p < 0.0001).
Seventy-one percent of dasatinib treated patients compared to 78% of imatinib treated patients experienced at least one adverse drug reaction. Overall incidences of grade 3-4 toxicity were 7.8% among patients treated with dasatinib compared to 7.0% with imatinib. Common adverse reactions reported more frequently on the dasatinib arm compared to the imatinib arm include anemia, cough, dyspnea, headache, neutropenia, pleural effusion, and thrombocytopenia.
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