CHICAGO—In patients with newly diagnosed chronic myelogenous leukemia in chronic phase (CML-CP), treatment with dasa-tinib showed significantly higher and faster rates of complete cytogenetic response and major molecular response at 12 months compared with imatinib, according to data reported here at the ASCO Annual Meeting.
“Given the predictive value of 12-month complete cytogenetic response and major molecular response and the favorable tolerability of dasatinib, dasatinib may improve long-term outcomes in patients with newly diagnosed CML-CP, and it may become a viable option in newly diagnosed disease,” said principal investigator Hagop M. Kantarjian, MD, Chairman and Professor of the Department of Leukemia at the University of Texas MD Anderson Cancer Center.
Patients taking the second-generation tyrosine kinase inhibitor also had a lower rate of progression—1.9% vs imatinib at 3.5%, he said.
The data were published in the New England Journal of Medicine (2010;362:2260–2270) on the same day as Dr. Kantarjian’s ASCO report (June 5). The study was supported by Bristol-Myers Squibb, which makes dasatinib under the trade name Sprycel.
As background, Dr. Kantarjian noted that once-daily dasatinib, a BCR-ABL kinase inhibitor, had already been proven effective in patients with CML-CP after imatinib failure, with a 73% rate of progression-free survival and 87% for overall survival at three years.
The study, called DASISION—Dasatinib versus Imatinib Study in Treatment-Naïve CML Patients—included 519 patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase, randomly selected to receive either dasatinib at 100 mg daily (259 patients) or imatinib at 400 mg daily (260 patients). The study took place in 108 centers in 26 countries.
As of the time of the report, 85% of dasatinib patients and 81% of imatinib patients remained on study.
At five years, the confirmed complete cytogenetic response rate was superior for dasatinib—77% vs 66% for imatinib, Dr. Kantarjian reported.
Similarly, the 12-month complete cytogenetic response rate was higher for dasatinib (83% vs 72%), as was the major molecular response rate (46% vs 28%).
“Complete cytogenetic responses and major molecular responses were obtained significantly faster with dasatinib,” Dr. Kantarjian said.
The rates of transformation to the accelerate phase or blast crisis were 1.9% (five patients) for dasatinib and 3.5% (nine) for imatinib.
In terms of toxicity, the rate of Grade 3/4 anemia was similar for both groups—10% for dasatinib vs 7% for imatinib—as was neutropenia—21% vs 20%, respectively. But the rate of thrombocytopenia was more common for dasatinib, at 19% vs 10%; there were no Grade 3/4 pleural effusions.
Dr. Kantarjian was asked in an interview for this article what data clinical oncologists will want to see before considering dasatinib over imatinib for first-line treatment, once it is approved. He said CML experts and community oncologists have differing opinions about the potential use of these drugs in front line.
“The question of their use becomes very much dependent on the comfort zone of the physician and patient about long-term versus short-term follow-up, differential toxicities, and the differential in cost.”
He noted that a year’s treatment with imatinib (Gleevec) today costs $40,000 to $50,000, and dasatinib and erlotinib are $65,000 to $70,000—not all that different.
“But five years down the road Gleevec will become generic and the price could go under $20,000 a year,” he said. “So the question is: how much more money do you pay for what kind of difference in the long term?”
Sonali Smith, MD, co-moderator of a news conference where Dr. Kantarjian’s study was discussed, said that the short follow-up period is one caveat with this report, although a cytogenetic response is still a very good surrogate marker for how patients will do in the future.
“Another issue is that we don’t have long-term survival, and since these patients are living for many years we won’t have that data for quite some time,” she said.
Dr. Smith also noted that other second-generation tyrosine kinase inhibitors have also been tested in this setting against imatinib for patients with newly diagnosed but previously untreated CML.
At the present time, she said, the two major challenges in treating CML are primary resistance to imatinib, and secondary resistance or intolerance to imatinib.
“That makes this study data profound, in that it gives our patients another option for front-line management, and continues to further our efforts to develop personalized treatments for these patients,” Dr. Smith said.
The other co-moderator, Lynn M. Schuchter, MD, Professor of Medicine and Chief of Hematology/Oncology at the University of Pennsylvania, added in explaining why the study was included in the news conference, that even though it may seem too soon to emphasize the data in that highlighted way for a study with such a short follow-up, it is “an amazing proof of principal—and this pathway also appears to be relevant in may other cancers. So that is why we thought it important to highlight this study.”