Dasatinib compared to imatinib (IM) in patients (pts) with newly diagnosed chronic-phase chronic myelogenous leukemia in chronic phase (CML-CP): Twelve-month efficacy and safety from the phase III DASISION study.

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LBA6500 Background: Dasatinib is a highly potent BCR-ABL kinase inhibitor. Once daily dasatinib demonstrated high rates of durable complete cytogenetic response (CCyR) with 73% progression-free survival and 87% overall survival at 3 yrs in pts with CML-CP post IM failure. DASISION compares efficacy and safety of dasatinib and IM as initial treatment of CML-CP. Methods: 519 pts with Ph(+) newly diagnosed CML-CP stratified by Hasford risk were randomized to dasatinib 100 mg QD (n = 259) or IM 400 mg QD (n = 260). The primary endpoint was 12-mo rate of confirmed CCyR (cCCyR; CCyR on 2 consecutive analyses; any # of metaphases). Other endpoints were rates of and times to CCyR and major molecular response (MMR). Results: Pts characteristics were well balanced. Minimum follow-up was 12 mos; median treatment duration was 14 mos. 85% of dasatinib and 81% of IM pts remained on study. Median dose intensity was 99 mg/d for dasatinib and 400 mg/d for IM. cCCyR rate was superior for dasatinib vs IM (77% vs 66%, P = 0.0067). 12-mo CCyR and MMR rates ( Table ) were higher for dasatinib vs IM (CCyR: 83% vs 72%; MMR: 46% vs. 28%). MMR was obtained significantly faster with dasatinib (HR 2.0, P < 0.0001) as was CCyR (HR 1.5, P < 0.0001). Rates of transformation to AP/BC were 1.9% for dasatinib and 3.5% for IM. Grade 3/4 anemia (10% vs 7%) and neutropenia (21% vs 20%) were similar across arms; thrombocytopenia was more common for dasatinib (19% vs. 10%). Non-hematologic adverse drug reactions (all grades) in ≥10% of pts (dasatinib vs. IM) were fluid retention (19% vs 42%; including pleural effusion, all grade 1 or 2, 10% vs. 0%), nausea (8% vs. 20%), vomiting (5% vs. 10%), myalgia (6% vs.12%), muscle inflammation (4% vs. 17%) and rash (11% vs. 17%). Conclusions: Dasatinib showed significantly higher and faster rates of CCyR and MMR vs IM. Given the predictive value of 12-mo CCyR and MMR and the favorable tolerability of dasatinib, dasatinib may improve long-term outcomes in pts with newly diagnosed CML-CP. [Table: see text] [Table: see text]