Dasatinib Shows Superior Efficacy and Acceptable Tolerability, Supporting First-Line Use in Newly Diagnosed CML-CP

CHICAGO—The BCR-ABL kinase inhibitor dasatinib achieved significantly higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) than imatinib as first-line treatment in patients with previously untreated chronic myeloid leukemia (CML), according to 24-month follow-up results from the randomized Phase 3 DASISION trial reported at the American Society of Clinical Oncology's 2011 Annual Meeting.

Hagop Kantarjian, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues, treated 516 patients with dasatinib 100mg once daily (n=258) or imatinib 400mg once daily (n=258). The primary endpoint was confirmed CCyR (cCCyR) at 12 months. After a median 28.1 months follow-up (range 0.1–40.1), 77% and 75% remained dasatinib or imatinib. The 24-month response rates for dasatinib compared with imatinib were: cCCyR 86% vs. 82%; CCyR 86% vs. 82%; and MMR 64% versus 46%, (P<0.0001), respectively.MMR occurred more often with dasatinib in all Hasford groups (the Hasford score being based on age, spleen size, blast count, platelet count, eosinophil count, and basophil count). A greater proportion of patients in the dasatinib group achieved undetectable levels of disease (defined as a CMR ≤0.0032% BCR-ABL on the International Scale). In time-to-response analyses, dasatinib patients were 1.7-fold more likely to have MMR and 1.5-fold more likely to have CCyR (P<0.0001 for both comparisons). For the dasatinib group vs. the imatinib group, 2.3% (n=6) vs. 5.0% (n=13) patients transformed to accelerated/blast phase (AP/BP) while on study; when follow-up beyond discontinuation of initial treatment was included, transformation to AP/BP) was 9 (3.5%) in the dasatinib group and 15 (5.8%) in the imatinib group.

The respective 24-month rates for dasatinib and imatinib were overall survival: 95.3% and 95.2%; progression-free survival (no AP/BP or loss of response): 93.7% and 92.1%; failure-free survival: 91.2% and 87.8.  Survival data remain immature; all patients, including those who discontinue, will be followed for five years.

Grade 3 or 4 nonhematologic adverse event incidences were ≤1%. Pleural effusions were observed only with dasatinib (13.6% for Grade 1 and 2 (n=35); <1% (n=2) for Grade 3) and did not appear to affect efficacy. Most cytopenias occurred within the first year. Grades 3 and 4 laboratory abnormality rates were ≤3% except hypophosphatemia (dasatinib 5%; imatinib 24%). Comparing dasatinib with imatinib, 59% vs. 43% experienced dose interruption, 28% vs. 15% experienced dose reduction and 7% vs. 5% discontinued due to drug-related side effects.

Study authors concluded that at 24 months, dasatinib 100mg once daily continues to show superior efficacy over imatinib with acceptable tolerability, hence supporting its first-line use in patients with newly diagnosed CML-CP.