Five-Year Results Support First-Line Dasatinib Use in CML

A 5-year analysis of the DASISION trial showed that dasatinib continued to offer better responses than imatinib in patients with chronic myeloid leukemia (CML), with good survival outcomes and no new or unexpected adverse events.

Initial results of the same trial showed superior efficacy with dasatinib over imatinib, with an acceptable safety profile, which led to its approval as a first-line agent. “In subsequent analyses, dasatinib continued to demonstrate deep and fast responses,” wrote study authors led by Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston. “Progression-free survival (PFS) and overall survival (OS) remained high and comparable between dasatinib and imatinib.”

The new 5-year report is the final analysis from this trial. DASISION included newly diagnosed chronic phase CML patients randomized to either dasatinib 100 mg once daily (259 patients) or imatinib 400 mg once daily (260 patients). The results were published in the Journal of Clinical Oncology.

The cumulative 5-year major molecular response rate (MMR) was 76% with dasatinib and 64% with imatinib (P = .0022). The MR^4.5 rate was 42% with dasatinib and 33% with imatinib (P = .0251).

Survival outcomes remained similar between the groups. The 5-year OS rate for dasatinib was 91%, compared with 90% for imatinib. “The age-adjusted life expectancy for patients with chronic phase CML in both arms of DASISION approached that for patients from an external, non-CML population,” the authors wrote. PFS rates were also similar between treatment groups, with a 5-year PFS of 85% with dasatinib and 86% with imatinib.

More patients in the dasatinib group achieved BCR-ABL1 ≤ 10% at 3 months (84% vs 64%). Those patients who did achieve that milestone were more likely to achieve MMR, MR^4.5, and complete cytogenetic response by 5 years, and also had higher 5-year OS and PFS rates.

The new analysis uncovered no new adverse events for either drug. Of all adverse events reported, 15% of those with dasatinib and 11% of those with imatinib were grade 3 or 4. Drug-related adverse events leading to discontinuation occurred in 16% of dasatinib patients and 7% of imatinib patients. Notably, drug-related pleural effusion was more common with dasatinib, occurring in 28% compared with 0.8% of imatinib patients. The authors noted that pleural effusion did not impair patients’ ability to obtain a response.

BCR-ABL1 mutations did not develop commonly in either treatment group; they were identified in 8% of dasatinib patients and 9% of imatinib patients at treatment or study discontinuation.

“These results suggest that first-line dasatinib should continue to be considered a standard first-line therapy for patients with newly diagnosed chronic phase CML,” the authors concluded, adding that other randomized studies have confirmed the benefit of dasatinib as well.