SPIRIT 2: Dasatinib Superior to Imatinib in Newly Diagnosed CML

Results from a large phase 3 prospective randomized open-label trial comparing imatinib 400 mg with dasatinib 100 mg daily were presented by Stephen O’Brien, MD, professor of hematology, Newcastle University Medical School, Newcastle upon Tyne, England. He presented the results of SPIRIT 2, which compared the 2 drugs in patients with newly diagnosed chronic myelogenous, at the 56th Annual Meeting of the American Society of Hematology, held in San Francisco.

According to Dr O’Brien, the SPIRIT 2 trial design was similar to the DASISION trial. The trial recruited 814 patients at 172 hospitals across England and in Northern Ireland, between August 2008 and March 2013. The primary endpoint of the trial was event-free survival at 5 years. Key secondary endpoints listed in the trial were the rate of achievement of a BCR-ABL/ABL ratio of <0.1% (major molecular response, MMR), cytogenetic response, and toxicity. The trial had an even distribution of patients between the 2 arms.

With a median follow up of 37.4 months a total of 300 patients have discontinued study medication, said Dr O’Brien—170 (7 deaths while on treatment) in the imatinib arm and 130 (5 deaths while on treatment) in the dasatinib arm. Following discontinuation, 11 patients from the imatinib arm and 15 from the dasatinib arm died. The research group is currently following 124 of these patients in the imatinib arm and 89 in the dasatinib arm.

While there were no unexpected side effects observed, Dr O’Brien said that patients receiving imatinib experienced GI toxicity more often than patients receiving dasatinib; fatigue, rash and headache were more common with dasatinib. A higher rate of grade 3/4 thrombocytopenia was observed in the dasatinib arm. Pleural effusions occurred in 78/406 (19.2%) patients on dasatinib, and 13 of 78 (16.7%) patients required drainage. No significant differences in cardiovascular adverse events were observed, he noted.

While significant differences in major cytogenetic response and complete cytogenetic response were observed, with dasatinib presenting a better effect, Dr O’Brien cautioned that a large amount of data was missing in this analysis, which could, in reality, render the difference insignificant.

Dr O’Brien concluded that dasatinib-treated patients have a higher rate of molecular response at 1 year but, with a median follow up of 37.4 months, there is no significant difference in rates of disease progression or overall survival. He suggested the need for additional follow up to evaluate differences in event free survival at 5 years, if any.