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Approved as a second-line agent, dasatinib induced rapid complete cytogenetic responses in most newly diagnosed patients with chronic-phase chronic myeloid leukemia in a small phase II trial.
A complete cytogenetic response was achieved by 24 of 31 (77%) evaluable patients at 3 months, 24 of 26 (92%) patients at 6 months, and 20 of 21 (95%) at 12 months, Dr. Ehab L. Atallah reported.
The off-label use of oral dasatinib (Sprycel) produced faster cytogenetic responses than have been observed historically with the current front-line use of imatinib, according to Dr. Atallah, an oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.
Among 50 M.D. Anderson patients who used 400 mg of imatinib daily, 54% achieved a complete cytogenetic response at 6 months and 65% at 12 months.
Those rates were 82% and 86%, respectively, among 205 patients who received 800 mg of imatinib daily.
Dasatinib was approved last year for patients in the chronic phase of chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib. It is marketed by the study's sponsor Bristol-Myers Squibb.
Imatinib (Gleevec) is approved for adults in all phases of CML.
The investigators randomized 35 patients with no prior therapy or less than 1 month of interferon-a or imatinib to 100 mg of dasatinib taken either once daily or in two 50-mg doses per day.
Dose escalation to 140 mg per day and 180 mg per day for poor response was allowed, as was dose reduction to 80 mg per day and 40 mg per day because of toxicity. Median follow-up was 9 months (range 1-18 months).
The study's primary end point of major molecular response at 12 months was similar to that of historical controls for 400 mg of imatinib per day (24%) and 800 mg of imatinib per day (47%), Dr. Atallah said.
Major molecular response defined by a BCR-ABL/ABL ratio of 0.05% or less was achieved in 6 of 22 (27%) evaluable patients in the study, which was led by principal investigator Dr. Jorge Cortes, also of M.D. Anderson.
More of the patients dosed once daily achieved a major molecular response than did those dosed twice daily (four patients vs. two).
At 12 months, just one patient achieved a complete molecular response as defined by an undetectable BCR-ABL/ABL ratio. This is acceptable, as the rate of complete molecular remission at 12 months is 5% with the standard dose of imatinib, Dr. Atallah said in an interview.
Hematologic adverse events included grade 3/4 thrombocytopenia (11%), grade 3/4 neutropenia (3%), and grade 3/4 anemia (6%). Fifteen of the 35 patients (43%) had to temporarily stop treatment. Reasons for treatment interruption included myelosuppression (four patients), plural effusion (three), rash (three), headache (two), fever (two), and other (four), said Dr. Atallah, who reported no conflict of interests related to this study.
ASCO discussant Dr. Charles A. Schiffer, professor of oncology and medicine at Karmanos Cancer Institute, Wayne State University, Detroit, said that while the data show that dasatinib produces rapid and high rates of response, they also beg the question, "Does it matter how fast you get there as long as you get there? Because there are some data that show that as long as you get to a complete cytogenetic response and molecular response with imatinib, you may do nearly as well as people who get there more rapidly. So these will be complex comparative trials in the future."
Atallah E.L. et al. Use of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in chronic phase (CML-CP). Abstract 70.