VIENNA (FRONTLINE MEDICAL NEWS) – Patients with chronic-phase chronic myeloid leukemia treated with first-line dasatinib achieved significantly more molecular responses at 2 years than those treated with imatinib in the SPIRIT 2 trial.

So far there is no difference, however, in disease progression or overall survival in the ongoing phase III trial, Dr. Stephen O’Brien reported at the annual congress of the European Hematology Association.

With 814 patients, SPIRIT 2 is the largest randomized trial of dasatinib (Sprycel) vs. imatinib (Gleevec).

Its design is similar to the ongoing 519-patient DASISION trial , which reported higher response rates with dasatinib than imatinib in the same setting, but similar progression-free and overall survival rates at 3-year follow-up.

The primary endpoint of SPIRIT 2 is event-free survival at 5 years and will be available in March 2018, he said. Patients at 172 hospitals in the United Kingdom were evenly randomized to imatinib 400 mg daily or dasatinib 100 mg daily. One patient in each group was excluded due to protocol violation or withdrawal of consent. Median follow-up is 42.4 months.

At 24 months, 60.6% of imatinib patients (246/406) and 71.4% of dasatinib patients (290/406) remained on treatment.

Significantly more patients treated with dasatinib than imatinib achieved a complete cytogenetic response at 12 months (53.3% vs. 42%; P = .003), but the difference was diminished at 24 months (33.7% vs. 27.5%; P = .189). These results should be interpreted with caution, however, because the data were incomplete, Dr. O’Brien , of Newcastle University Medical School, Newcastle upon Tyne, England, said.

He noted that the molecular data are more reliable and were calculated based on samples drawn within a 6-week window on either side of the 24-month time point. Values had to be imputed for 22 patients who had no 24-month sample taken, although this imputation should not impact survival outcomes, he said. Major molecular response was defined as a 3-log reduction in the BCR-ABL/ABL ratio, relative to baseline, with data also captured for patients achieving a 4-log reduction.

Significantly more patients on dasatinib than imatinib achieved an MR3 response (57.5% vs. 46%; P < .001) and MR4.5 response (20.2% vs. 14.3%; P = .026).

More patients stopped imatinib than dasatinib due to investigator and/or patient concerns about inadequate response (10.8% vs. 1.3%), whereas nonhematologic toxicities drove more patients to abandon dasatinib (22% vs. 12%), according to Dr. O’Brien.

Pleural effusion, a known toxicity with dasatinib, occurred in 24.1% of patients given the drug vs. 1.2% given imatinib, requiring drainage in 22 cases vs. 1 case, respectively. There was also a “difficult-to-explain” signal for breathlessness with no obvious cause (15.5% vs. 8%). Hypertension was confirmed in only one of these cases and symptoms resolved in others when the drug was withdrawn, he said.

Serious cardiac adverse events were reported in 2.2% of patients in the imatinib arm and 4.2% in the dasatinib arm. Again, the results should be interpreted with caution because trials set up at the time of SPIRIT2 in 2008 were not designed to look carefully at this outcome, Dr. O’Brien observed.

In all, 38 patients have died; 19 in each group.

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