Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study

Authors


  • Statement of prior presentation: Presented at the 50th annual meeting of the American Society of Hematology, San Francisco, CA, December 6–9, 2008 (Larson R, et al., Blood 2008; 112:abstract 2926) and at the 12th Congress of the European Haematology Association, Vienna, Italy, June 7-10, 2007 (Dombret H, et al., Haematologica 2007;92 (Suppl. 1):abstract 859).

  • Conflict of interest: MBL received research grant from Bristol-Myers Squibb; OGO received honoraria/consulting fee and research grant from Bristol-Myers Squibb; NPS received consulting fee from Bristol-Myers Squibb; RAL received consulting fee and research grant from Bristol-Myers Squibb; JJR, GE, MCM, and AC have no financial relationships to disclose; EB received honoraria from Bristol-Myers Squibb; HD received honoraria/consulting fee from Bristol-Myers Squibb; MBB-G and CZ are employees of Bristol-Myers Squibb; GM has no financial relationships to disclose.

Abstract

Dasatinib 70 mg twice daily is indicated for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) intolerant or resistant to imatinib. In patients with chronic-phase chronic myelogenous leukemia, once-daily dosing has similar efficacy with improved safety, compared with twice-daily dosing. A phase 3 study (n = 611) assessed the efficacy and safety of dasatinib 140 mg once daily versus 70 mg twice-daily in patients with advanced phase chronic myelogenous leukemia or Ph+ ALL resistant or intolerant to imatinib. Here, results from the Ph+ ALL subset (n = 84) with a 2-year follow-up are reported. Patients were randomly assigned to receive dasatinib either 140 mg once daily (n = 40) or 70 mg twice daily (n = 44). The rate of confirmed major hematologic response with once-daily dosing (38%) was similar to that with twice-daily dosing (32%). The rate of major cytogenetic response with once-daily dosing (70%) was higher than that with twice-daily dosing (52%). Compared with the twice-daily schedule, the once-daily schedule had longer progression-free survival (median, 3.0 months versus 4.0 months, respectively) and shorter overall survival (median, 9.1 months versus 6.5 months, respectively). Overall safety profiles were similar between two groups, with nonhematologic adverse events being mostly grade 1 or 2. Pleural effusion was less frequent with once-daily dosing than with twice-daily dosing (all grades, 18% versus 32%). Notably, none of the differences between the two schedules was statistically significant. Compared with the 70 mg twice daily, dasatinib 140 mg once daily had similar overall efficacy and safety in patients with imatinib-resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier: NCT00123487). Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc.

Ancillary