Five-year follow-up results were presented today at the 16th Congress of the European Hematology Association (EHA) in London from a Phase 3 randomised, open-label, dose-optimisation study of dasatinib (Sprycel?,Bristol-Myers Squibb), an oral BCR-ABL inhibitor, in Philadelphia chromosome-positive (Ph+) chronic-phase chronic myeloid leukaemia(CP-CML) adult patients resistant or intolerant to imatinib mesylate.

CML is a slow-growing type of leukaemia in which the body produces an uncontrolled number of abnormal white blood cells.[1] CML accounts for 15% of all leukaemias.[2] Due to the ageing population, the incidence of CML is increasing. The incidence is estimated at 1-2 cases per 100,000.[3]

CML occurs when pieces of two different chromosomes break off and attach to each other. The new chromosome is called the Philadelphia-positive chromosome, which contains an abnormal gene called BCR-ABL that signals cells to make too many white blood cells. There is no known cause for the genetic change that causes CML.

Progression-free survival
At five years, for patients randomised to receive dasatinib 100 mg once daily (n=167), overall survival was 78% (95% CI: 72%-85%) and progression-free survival was 57% (95% CI: 48%-67%). Five percent of patients (n=8) randomised to dasatinib 100 mg once daily progressed to accelerated or blast phase on study at five years of follow-up.

The five-year safety data from this study are consistent with the previously-reported safety profile of dasatinib 100 mg once daily. The cumulative incidence of grade 3/4 pleural effusion was 4%. Other grade 3/4 adverse events (AEs) with cumulative rates greater than or equal to 5% included neutropenia (36%), thrombocytopenia (24%), leukopenia (18%), and anaemia (13%). The cumulative incidence rates of the most common non-hematological AEs of all grades at five years of follow-up were: headache (33%), diarrhoea (28%), fatigue (26%), dyspnea (24%) and pleural effusion (24%).

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Study design
Study CA180-034 was designed to assess the efficacy and safety of dasatinib 100 mg once daily. The trial enrolled 670 CP-CML patients with resistance (n=497) or intolerance (n=173) to imatinib who were randomised to one of four treatment arms: 100 mg once daily (n=167), 50 mg twice daily (n=168), 140 mg once daily (n=167), and 70 mg twice daily (n=168). In this heavily pre-treated population, the median time from onset of CML to randomisation in patients on the 100mg once daily arm was 55 months and 46% of these patients had more than three years of prior imatinib treatment. Data on the primary endpoint of the study, major cytogenetic response in imatinib-resistant patients, have been previously reported. Thirty-four percent of patients randomised to receive dasatinib 100 mg once daily remained on treatment at 5 years.

Long term efficacy
“In this study, the five-year follow up data demonstrated the long-term efficacy and consistent safety profile for SPRYCEL 100 mg once daily in patients with CP-CML following prior imatinib therapy,” said Neil Shah, MD, PhD, Assistant Professor, Division of Hematology/Oncology, University of California, San Francisco and principal investigator of the study. “Results from this Sprycel study are important as they provide long-term follow up of patients with CP-CML treated with Sprycel who are resistant or intolerant to imatinib.”

[1] Macmillan Cancer Support. Leukaemia Overview. Last accessed April 2011
[2] National Comprehensive Cancer Network (NCCN). Chronic Myelogenous Leukemia – Clinical Practice Guidelines in Oncology – v.1.2007.
[3] Baccarani, M. and Dreyling, M. Annals of Oncology. 2010;21:165-167.

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