ORLANDO, FLA—Results from the SO325 Intergroup Trial offered further evidence that dasatinib (Sprycel) is more efficacious than imatinib (Gleevec) in newly diagnosed chronic myeloid leukemia (CML-CP). The phase II trial compared 100 mg of dasatinib vs 400 mg imatinib.
Investigators compared molecular response rates (decreases in Bcr-Abl transcript) among patients with previously untreated CML-CP who were treated with either agent and estimated cytogenetic and hematologic response rates with the two regimens. Each trial arm included 245 evaluable patients, with an even distribution in Hasford low/intermediate risk categories, said presenter Jerald P. Radich, MD, from the Fred Hutchinson Cancer Research Center, University of Washington in Seattle.
Doses were escalated in 2% of subjects in the dasatinib arm and 3% in the imatinib arm. Doses were reduced or interrupted in 35% and 49% in the dasatinib and imatinib groups, respectively. Removal from protocol treatment was more common in the imatinib group (37% vs 27%).
Among cases of discontinuation due to toxicities (15% dasatinib vs 11% imatinib), nonhematologic toxicities were by far the most common. With dasatinib, pleural effusion (14/122 vs 2/123 in imatinib arm) and headache (34/122 vs 19/123) were more common. With imatinib, fluid retention (59/123 vs 24/122 in dasatinib arm), nausea (59/123 vs 32/122) and muscle pain (44/123 vs 12/122) were more frequent. Progression to accelerated or blast phase was reported in 1% of patients in the dasatinib group and 3% in the imatinib group (ASH 2010 abstract LBA-6).
The median Bcr-Abl reductions at one year were greater with dasatinib at 100 mg/day than with imatinib at 400 mg/day (3.3 log vs 2.8 log; P = .048). While 4.5-log reductions (21% dasatinib vs 14% imatinib) and 4-log reductions (27% dasatinib vs 20% imatinib) were similar between the two agents, 3-log reductions in Bcr-Abl were significantly more frequent with dasatinib (43% vs 59%; P = .042).
Complete hematologic responses were reported within 12 months for 86% in the dasatinib arm and 90% in the imatinib arm. Complete cytogenetic responses were reported within 12 months for 82% of patients in the dasatinib group and 69% in the imatinib group (P = .097). Twelve-month overall survival was similar for both groups at 99% and 100%, respectively. Progression-free survival at 12 months was 99% for dasatinib and 96% for imatinib. There were four deaths in the dasatinib group (one attributed to CML) and three in the imatinib group (two attributed to CML).
Dr. Radich noted that the SO325 finding of deeper responses with dasatinib were consistent with the DASISION trial analysis. “SO325 provides further evidence that dasatinib is more efficacious than imatinib 400 mg in newly diagnosed chronic phase CML,” he said.
He pointed out that incomplete data collection at the time of the ASH presentation impaired any subgroup analyses. “The relationship of progression to resistance suggests a rationale for stronger Bcr-Abl inhibition induced earlier,” he said, adding that the promise of complete molecular remissions as a gateway to discontinuation of treatment gave compelling support for achieving stronger Bcr-Abl inhibition.
Commenting on the study, Robert Hromas, MD, chief of hematology oncology at the University of New Mexico in Albuquerque, commented, “I think a better molecular response will indeed eventually correlate with better outcomes. I believe that dasatinib upfront is the appropriate therapy currently.”
“The Holy Grail in CML is discontinuing therapy,” Dr. Hromas said. “To get a complete molecular response, you need to add something to dasatinib or imatinib like an HDAC inhibitor. Others have added other molecules to dasatinib in an attempt to get the CML stem cell to differentiate. At that point, [CML] is more sensitive to the dasatinib or imatinib.”