TY - JOUR
T1 - Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes
T2 - a randomised, open-label, phase III study
AU - for the International Vidaza High-Risk MDS Survival Study Group
AU - Fenaux, Pierre
AU - Mufti, Ghulam J.
AU - Hellstrom-Lindberg, Eva
AU - Santini, Valeria
AU - Finelli, Carlo
AU - Giagounidis, Aristoteles
AU - Schoch, Robert
AU - Gattermann, Norbert
AU - Sanz, Guillermo
AU - List, Alan
AU - Gore, Steven D.
AU - Seymour, John F.
AU - Bennett, John M.
AU - Byrd, John
AU - Backstrom, Jay
AU - Zimmerman, Linda
AU - McKenzie, David
AU - Beach, CL L.
AU - Silverman, Lewis R.
N1 - Funding Information:
The research was sponsored by Celgene Corporation. Neil Malone, an employee of Celgene, provided independent consultation for the writing of the paper. James W Vardiman provided adjudication of central pathology review and Anne Hagemeijer did the central cytogenetics review. Kenneth J Kopecky and Gary G Koch provided independent review of the statistical analysis plan describing the statistical approaches; and Gary G Koch provided independent review of the analyses, interpretation of the results, and the written paper.
PY - 2009/3
Y1 - 2009/3
N2 - Background: Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods: In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m2 per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French-American-British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings: Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1-26·9), median overall survival was 24·5 months (9·9-not reached) for the azacitidine group versus 15·0 months (5·6-24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43-0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1-58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7-34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most common grade 3-4 adverse events for all treatments. Interpretation: Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care. Funding: Celgene Corporation.
AB - Background: Drug treatments for patients with high-risk myelodysplastic syndromes provide no survival advantage. In this trial, we aimed to assess the effect of azacitidine on overall survival compared with the three commonest conventional care regimens. Methods: In a phase III, international, multicentre, controlled, parallel-group, open-label trial, patients with higher-risk myelodysplastic syndromes were randomly assigned one-to-one to receive azacitidine (75 mg/m2 per day for 7 days every 28 days) or conventional care (best supportive care, low-dose cytarabine, or intensive chemotherapy as selected by investigators before randomisation). Patients were stratified by French-American-British and international prognostic scoring system classifications; randomisation was done with a block size of four. The primary endpoint was overall survival. Efficacy analyses were by intention to treat for all patients assigned to receive treatment. This study is registered with ClinicalTrials.gov, number NCT00071799. Findings: Between Feb 13, 2004, and Aug 7, 2006, 358 patients were randomly assigned to receive azacitidine (n=179) or conventional care regimens (n=179). Four patients in the azacitidine and 14 in the conventional care groups received no study drugs but were included in the intention-to-treat efficacy analysis. After a median follow-up of 21·1 months (IQR 15·1-26·9), median overall survival was 24·5 months (9·9-not reached) for the azacitidine group versus 15·0 months (5·6-24·1) for the conventional care group (hazard ratio 0·58; 95% CI 0·43-0·77; stratified log-rank p=0·0001). At last follow-up, 82 patients in the azacitidine group had died compared with 113 in the conventional care group. At 2 years, on the basis of Kaplan-Meier estimates, 50·8% (95% CI 42·1-58·8) of patients in the azacitidine group were alive compared with 26·2% (18·7-34·3) in the conventional care group (p<0·0001). Peripheral cytopenias were the most common grade 3-4 adverse events for all treatments. Interpretation: Treatment with azacitidine increases overall survival in patients with higher-risk myelodysplastic syndromes relative to conventional care. Funding: Celgene Corporation.
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U2 - 10.1016/S1470-2045(09)70003-8
DO - 10.1016/S1470-2045(09)70003-8
M3 - Article
C2 - 19230772
AN - SCOPUS:62849104641
SN - 1470-2045
VL - 10
SP - 223
EP - 232
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 3
ER -