Bristol-Myers Squibb is progressing plans to take Sprycel into front-line treatment for patients with chronic myelogenous leukaemia in chronic phase (CML-CP) following the presentation of promising data at the European Haematology Association meeting in Vienna, Austria.
According to updated results from the ongoing study, Sprycel (dasatinib) is safe and effective in treatment-naïve patients, achieving rapid, complete cytogenetic responses in a high percentage of patients with previously untreated CML-CP.
Dr Claude Nicaise, head of clinical development for dasatinib at B-MS in the USA, said that the company would discuss the results, and the design of new large long-term global studies to investigate the potential of dasatinib as first-line treatment in patients with CML-CP, with regulatory authorities in Europe and the USA.
In the study presented at the EHA, 34 patients received dasatinib orally at a dose of 100 mg/day, and were randomised to either a 50 mg-twice-daily or a 100 mg-once-daily schedule. Dose escalation to 140 mg/day and 180 mg/day for poor response or dose reduction to 80 mg/day and 40 mg/day for toxicity, maintaining the same schedule, was allowed.
Three-month results from 34 patients showed that complete haematologic response and major cytogenetic response both occurred in 23 (88%) of 26 evaluable patients and complete cytogenetic response in 20 (77%) pts. After six months of therapy, 24/26 (92%) evaluable patients had achieved complete cytogenetic response. According to the study authors, these results compare favourably with a complete cytogenetic response at six months of 54% with imatinib 400 mg/day and 85% with imatinib 800 mg/day, in historical data of similar patients treated in studies at the University of Texas MD Anderson Cancer Center.
At one year, 5/11 (45%) evaluable patients had achieved a major molecular response in the study reported at the EHA (one of which was complete). The most common non-hematologic adverse events included dyspnoea (8 pts), fatigue (7 pts), muscle pain (6 pts), and headache (5 pts) and were predominantly grade 1-2. Pleural effusion occurred in three patients (grade 1-2 in all). Grade 3-4 haematologic toxicity (transient) included anaemia in 4 pts, neutropenia in 7 pts, and thrombocytopenia in 4 pts. The actual median daily dose for all pts was 100mg and no difference in adverse events was observed between the two dose schedules used in the study. The investigators concluded that rapid, complete cytogenetic responses to dasatinib 100 mg/day were observed in a high percentage of patients with previously untreated CML-CP.
“Use of dasatinib front line may prevent the emergence of [Novartis' Gleevec] imatinib resistance. This may prove a good rationale for using the new tyrosine kinase inhibitors front line, but we need to ensure the toxicity profile is acceptable,” said study co-author Professor Hago Kantarjian, chairman of the department of leukaemia at MD Anderson. Dasatinib is currently licensed for use only in patients who are resistant or intolerant to prior treatment, including imatinib.