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. CML accounts for 15% of all leukaemias. Due to the ageing population, the incidence of CML is increasing. The incidence is estimated at 1-2 cases per 100,000.
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.
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%).
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.”
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 National Comprehensive Cancer Network (NCCN). Chronic Myelogenous Leukemia – Clinical Practice Guidelines in Oncology – v.1.2007.
 Baccarani, M. and Dreyling, M. Annals of Oncology. 2010;21:165-167.