A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial

The phase III AZA-001 study established that azacitidine significantly improves overall survival compared with conventional care regimens (hazard ratio 0.58 [95% confidence interval 0.43-0.77], P<0.001). This analysis was conducted to investigate the relationship between treatment response and overall survival. AZA-001 data were analyzed in a multivariate Cox regression analysis with response as a time-varying covariate. Response categories were "Overall Response" (defined as complete remission, partial remission, or any hematologic improvement) and "Stable Disease" (no complete or partial remission, hematologic improvement, or progression) or "Other" (e. g. disease progression). Achieving an Overall Response with azacitidine reduced risk of death by 95% compared with achieving an Overall Response with the conventional care regimens (hazard ratio 0.05 [95% CI: 0.01-0.43], P=0.006). Sensitivity analyses indicated that significantly improved overall survival remained manifest for patients with a hematologic improvement who had never achieved complete or partial remission (hazard ratio 0.19 [95% CI: 0.08-0.46], P<0.001). Stable Disease in both azacitidine-treated and conventional care-treated patients was also associated with a significantly reduced risk of death (hazard ratio 0.09, [95% CI: 0.06-0.15]; P<0.001). These results demonstrate azacitidine benefit on overall survival compared with conventional care regimens in patients with higher-risk myelodysplastic syndromes who achieve hematologic response but never attain complete or partial remission, in addition to the survival advantage conferred by achievement of complete or partial remission. This study was registered with clinicaltrials.gov (NCT00071799).