Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features.
Godfrey, Anna L
Campbell, Peter J
Wilkins, Bridget S
McMullin, Mary Frances
Green, Anthony R
Harrison, Claire N
United Kingdom Medical Research Council Primary Thrombocythemia-1 Study
United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup
French Intergroup of Myeloproliferative Neoplasms
the Australasian Leukaemia and Lymphoma Group.
J Clin Oncol
American Society of Clinical Oncology (ASCO)
MetadataShow full item record
Godfrey, A. L., Campbell, P. J., MacLean, C., Buck, G., Cook, J., Temple, J., Wilkins, B. S., et al. (2018). Hydroxycarbamide Plus Aspirin Versus Aspirin Alone in Patients With Essential Thrombocythemia Age 40 to 59 Years Without High-Risk Features.. J Clin Oncol, 36 (34), 3361-3369. https://doi.org/10.1200/JCO.2018.78.8414
PURPOSE: Cytoreductive therapy is beneficial in patients with essential thrombocythemia (ET) at high risk of thrombosis. However, its value in those lacking high-risk features remains unknown. This open-label, randomized trial compared hydroxycarbamide plus aspirin with aspirin alone in patients with ET age 40 to 59 years and without high-risk factors or extreme thrombocytosis. PATIENTS AND METHODS: Patients were age 40 to 59 years and lacked a history of ischemia, thrombosis, embolism, hemorrhage, extreme thrombocytosis (platelet count ≥ 1,500 × 109/L), hypertension, or diabetes requiring therapy. In all, 382 patients were randomly assigned 1:1 to hydroxycarbamide plus aspirin or aspirin alone. The composite primary end point was time to arterial or venous thrombosis, serious hemorrhage, or death from vascular causes. Secondary end points were time to first arterial or venous thrombosis, first serious hemorrhage, death, incidence of transformation, and patient-reported quality of life. RESULTS: After a median follow-up of 73 months and a total follow-up of 2,373 patient-years, there was no significant difference between the arms in the likelihood of patients reaching the primary end point (hazard ratio, 0.98; 95% CI, 0.42 to 2.25; P = 1.0). The incidence of significant vascular events was low, at 0.93 per 100 patient-years (95% CI, 0.61 to 1.41). There were also no differences in overall survival; in the composite end point of transformation to myelofibrosis, acute myeloid leukemia, or myelodysplasia; in adverse events; or in patient-reported quality of life. CONCLUSION: In patients with ET age 40 to 59 years and lacking high-risk factors for thrombosis or extreme thrombocytosis, preemptive addition of hydroxycarbamide to aspirin did not reduce vascular events, myelofibrotic transformation, or leukemic transformation. Patients age 40 to 59 years without other clinical indications for treatment (such as previous thrombosis or hemorrhage) who have a platelet count < 1,500 × 109/L should not receive cytoreductive therapy.
United Kingdom Medical Research Council Primary Thrombocythemia-1 Study, United Kingdom National Cancer Research Institute Myeloproliferative Neoplasms Subgroup, French Intergroup of Myeloproliferative Neoplasms, the Australasian Leukaemia and Lymphoma Group., Humans, Thrombosis, Disease Progression, Aspirin, Hydroxyurea, Prognosis, Treatment Outcome, Drug Therapy, Combination, Drug Administration Schedule, Severity of Illness Index, Proportional Hazards Models, Risk Assessment, Prospective Studies, Dose-Response Relationship, Drug, Internationality, Adult, Middle Aged, Australia, France, Ireland, New Zealand, Female, Male, Janus Kinase 2, Thrombocythemia, Essential, Kaplan-Meier Estimate, United Kingdom
Supported by the Medical Research Council, UK, Cancer Research UK, the French National Cancer Institute (INCa), Bloodwise, the Wellcome Trust, the Kay Kendall Leukaemia Fund, and the Leukemia and Lymphoma Society of America
Medical Research Council (MC_PC_12009)
External DOI: https://doi.org/10.1200/JCO.2018.78.8414
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282922
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/