7007 Background: The recommended dosing regimen of dasatinib for CML-CP is now 100 mg once daily (QD) (previously 70 mg twice daily [BID]), based upon a phase III dose-optimization study (CA180-034) that enrolled patients (pts) with CML-CP with resistance, intolerance, or suboptimal response to imatinib. While therapeutic milestones have been established for pts with CML-CP treated with imatinib, they have not been well established for pts treated with second-line TKIs.
METHODS
Pts were randomized using a 2 × 2 factorial design to one of four treatment arms: 100 mg QD (n = 167), 70 mg BID (n = 168), 140 mg QD (n = 167), or 50 mg BID (n = 168). Details of study design and endpoints have been described previously.
RESULTS
After a minimum of 24 months of follow-up, the 24-month PFS rate with 100 mg QD was 80% (vs. 75%-76% in other arms) and the overall survival rate was 91% (vs. 88%-94%). In all arms, high response rates were achieved in pts with or without a baseline BCR-ABL mutation. Dasatinib 100 mg QD was well tolerated and rates of key side effects showed only a minimal increment from 12 to 24 months. Among the four treatment arms, significant differences were observed in rates of drug-related pleural effusion (all grades: p = 0.049) and cytopenia (p = 0.003 for grade 3/4 thrombocytopenia), with lowest rates observed for 100 mg QD. Dasatinib 100 mg QD treatment resulted in the lowest rates of treatment interruption, reduction, and discontinuation. In addition to providing 36-month follow-up, the likelihood of achieving long-term endpoints based on cytogenetic status at 6, 12, and/or 18 months will be presented.
CONCLUSIONS
Dasatinib 100 mg once daily remains the optimal dosing schedule for pts with CML-CP. The landmark analyses to be presented should provide useful information to clinicians treating imatinib-resistant, -suboptimally responding, or -intolerant CML-CP pts with dasatinib 100 mg once daily based on cytogenetic response at key intervals. [Table: see text].