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Two-Year Data on Dasatinib Shows Continued Benefit in Patients With Chronic Myeloid Leukemia After Imatinib Failure: Presented at ASH

By John Gever

ATLANTA, GA -- December 12, 2007 -- Favorable short-term responses to dasatinib are maintained for up to 2 years in most patients with chronic myeloid leukemia (CML) who cannot be treated successfully with imatinib, according to follow-up data from the START-C study.

The results were presented here on December 11 at the 49th American Society of Hematology (ASH) Annual Meeting by Richard Stone, MD, Clinical Director, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

"Dasatinib does represent a major advance for patients who can't take imatinib because of intolerance or who shouldn't take imatinib because of resistance," Dr. Stone said.

The multicenter SRC/ABL Tyrosine kinase inhibition Activity Research Trials of dasatinib in chronic phase CML (START-C) trial enrolled 387 patients to be treated with 70 mg of dasatinib twice daily after showing resistance or having unacceptable adverse effects with imatinib.

After 1 year, the progression-free survival rate was 91% and overall survival rate was 97%. With 2 years of follow-up, Dr. Stone reported, the progression-free survival rate stands at 80% and overall survival rate is 94%.

Major cytogenetic response rate was 62% at the 2-year evaluation, an increase over the 58% rate seen at 6 months. Major molecular response was 47% after 2 years.

Prior to participating in START-C, patients had received up to 800 mg/day of imatinib. Ninety-nine of the patients were unable to tolerate imatinib and 288 either did not respond or lost a response. About half the patients overall had taken imatinib for more than 3 years.

Serious neutropenia and thrombocytopenia were common in the first year of treatment, Dr. Stone said, and the rate did not increase in the second year.

The type and frequency of nonhematologic grade 3 or 4 adverse effects were similar at the 1-year and 2-year evaluations. Pleural effusion, dyspnea, bleeding, diarrhea, musculoskeletal pain, and fatigue were the most common, each seen in 2% to 9% of patients.

Dr. Stone said dasatinib was effective in patients with 42 of 43 mutations in the BCR-ABL gene identified in baseline, and in patients with P-loop mutations. Those who had failed to obtain a cytogenetic response to imatinib also did well with dasatinib, he said.

"This drug is interesting because it can inhibit the mutant enzymes that are the reason for resistance to imatinib," Dr. Stone said, explaining that secondary mutations in BCR-ABL reduce its vulnerability to imatinib but not to dasatinib.

There was no evidence of cross-intolerance to dasatinib, as adverse effects were not markedly increased in patients who were intolerant to imatinib versus those with imatinib resistance.

The recommended dose of dasatinib has since been changed to 100 mg once daily, Dr. Stone noted, which appeared to be as effective and less toxic than the 70-mg twice-daily regimen used in this trial.

Phase 3 trials are now underway comparing dasatinib directly to imatinib as front-line treatment for chronic-phase CML.

Bristol-Myers Squibb, makers of dasatinib, provided funding for the START-C trial.


[Presentation title: Efficacy of Dasatinib in Patients With Chronic-Phase Chronic Myelogenous Leukemia With Resistance or Intolerance to Imatinib: 2-Year Follow-Up Data From START-C (CA180-013). Abstract 734]

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