CHICAGO—“Dasatinib 100 mg once daily should become frontline therapy in newly diagnosed chronic-phase chronic myelogenous leukemia,” said DASISION (Dasatinib versus Imatinib Study in Treatment-Naïve CML Patients; CA180-056) lead investigator Hagop M. Kantarjian, MD, The University of Texas, M. D. Anderson Cancer Center, Houston. Kantarjian’s statement was based on findings from the DASISION comparison of firstline dasatinib with first-line imatinib in patients with chronic-phase chronic myelogenous leukemia (CP-CML).
Imatinib is the current gold standard for CP-CML, Kantarjian pointed out in a presentation at the 2010 annual meeting of the American Society of Clinical Oncology. Once-daily dasatinib, in earlier research, has induced high rates of complete cytogenetic response (CCyR) and progression-free survival (PFS) in CML after imatinib failure. In vestigations also have shown that patients receiving imatinib who achieve a CCyR and a major molecular response (MMR) by 12 months have longer PFS and reduced risks of disease progression or death. MMR, the highest standard of response, was defined by the presence of ≤0.1% BCR-ABL transcripts. In a phase 2 study of first-line dasatinib, CCyR and MMR rates were high.
DASISION, a phase 3 study, was conducted at 108 centers in 26 countries among 519 patients (mean age, 47 years) with newly diagnosed CML. Patients were randomized to either dasatinib 100 mg/day (n = 259) or imatinib 400 mg/day (n = 260). Dose escalations to dasatinib 140 mg once daily and to imatinib 600 mg to 800 mg once daily were permitted for suboptimal response. Patients were all enrolled within 1 month of their initial diagnosis. Mean duration of therapy was 14 months. The primary end point was confirmed CCyR by 12 months, with confirmed CCyR defined as a CCyR detected in two consecutive assessments.
Dose escalations were reported in 5% of patients receiving dasatinib and in 14% of patients receiving imatinib. Data analyses revealed CCyRs in 83% and 72% of patients in the dasatinib and imatinib arms, respectively (P = .0011), and confirmed CCyRs in 77% and 66% of patients in the two groups, respectively (P = .0067) at 12 months. An analysis of CCyR rates at 3, 6, 9, and 12 months revealed that the likelihood of achieving a CCyR at all points remained at ~50% higher with dasatinib than with imatinib throughout (P <.001; hazard ratio, 1.53). MMR rates followed a similar pattern, with the 12-month rates at 46% for dasatinib 100 mg once daily and 28% for imatinib 400 mg once daily (P <.0001). Patients were twice as likely to achieve MMR at any time with dasatinib versus imatinib. Median time to achieving MMR was 6.3 months for dasatinib and 9.2 months for imatinib. Also, progression to accelerated or blast phase was less frequent with dasatinib (1.9%) than with imatinib (3.5%). No patients who achieved MMR progressed to accelerated or blast phase. Twelve-month overall survival was similar for both groups (dasatinib, 97.2%; imatinib, 98.8%).
Rates of thrombocytopenia and anemia were higher with dasatinib (thrombocytopenia, 19% vs 10%; anemia, 10% vs 7%). Neutropenia occurred in about 20% of patients with both agents. Adverse event–related discontinuations were low at 1.2% for dasatinib and 0.4% for imatinib. Discontinuations for treatment failure occurred in 5% of patients treated with dasatinib and 8.9% of those treated with imatinib. Pleural effusion was more common with dasatinib (10% vs 0%), and superficial edema was more common with imatinib (9% for dasatinib vs 36% for imatinib).
Kantarjian concluded that dasatinib 100 mg/day should be first-line therapy for newly diagnosed CP-CML and commented, “Based on the predictive value of complete cytogenetic responses, longer follow-up of first-line dasatinib may demonstrate better longterm outcomes than imatinib.”