Dasatinib or high-dose imatinib for patients with chronic myelogenous leukemia chronic-phase (CML-CP) resistant to standard- dose imatinib: 2-year follow-up data from START-R.

7012 Background: Resistance to imatinib is a well-recognized problem in CML-CP. Dasatinib is 325-fold more potent than imatinib against BCR-ABL in vitro is effective in imatinib-resistant CML patients. Prior to dasatinib, imatinib dose escalation to 800 mg/day was the primary option for resistance to standard-dose imatinib.,In this global Phase II study, 150 patients (pts) with CML-CP resistant to imatinib 400-600 mg/d were randomized 2:1 to dasatinib 70 mg BID (n=101) or imatinib 800 mg/d (n=49). The primary endpoint of the study was major cytogenetic response (MCyR) at 12 wks. Crossover was permitted for confirmed progression, lack of MCyR at 12 wks, or intolerance despite dose reduction. MCyR rates at 12 weeks were 36% vs 29%; p=0.4025. Two-year follow-up is now presented.,With a minimum follow-up (LPFV to database closure) of 24 mos, MCyR rates were (53% vs 33%, p=0.017) for pts receiving dasatinib and high-dose imatinib, respectively; the difference being attributable to complete cytogenetic responses (44% dasatinib vs 18% imatinib, p=0.0025). Major molecular responses (MMR) were also more frequent with dasatinib (29% vs 12%, p=0.028). Duration of MCyR was greater with dasatinib; 90% of dasatinib pts maintained MCyR at 18 mos vs 74% of imatinib pts. Analysis of progression-free survival at 24 mos favored dasatinib (86% vs 65%, p=0.0012); results were consistent irrespective of the prior imatinib dose received (400 mg/d, p=0.0562; 600 mg/d, p=0.0033). Time to treatment failure also favored dasatinib (proportion of pts without failure at 24 mos: 59% vs 18% p<0.0001). Grade 3-4 non-hematologic toxicity was minimal for both treatment groups. Grade 3-4 cytopenia was more frequent with dasatinib. Discontinuation attributable to toxicity occurred in 22% of pts receiving dasatinib and 20% treated with imatinib.,With an extended follow-up of 24 mos, the overall benefit-risk assessment favors dasatinib over high-dose imatinib in CML-CP pts with resistance to 400-600 mg imatinib. The current labelled dose of 100 mg QD was approved based on a subsequent Phase III dose optimization study which showed comparable efficacy with improved tolerability compared with 70 mg BID. [Table: see text].