my personal edition > myelodysplastic syndrome > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Hypomethylating Agents Show Better Efficacy Than Best Supportive Care in Patients With Myelodysplastic Syndrome: Presented at EHA

By Chris Berrie

BERLIN -- June 8, 2009 -- Hypomethylating agents show better efficacy than best supportive care (BSC) in patients with myelodysplastic syndrome (MDS), without showing treatment-related mortality (TRM), researchers reported here at the 14th Congress of the European Hematology Association (EHA).

Moreover, 5-azacytidine (AZA-C) provides significantly better overall survival (OS) than decitabine.

The systematic review and meta-analysis was presented by principal investigator Benjamin Djulbegovic, MD, Medicine and Oncology, Moffit Cancer Centre, University of South Florida, Tampa, Florida, here on June 6.

"Until the hypomethylating agents, there was nothing really for treatment of MDS, as no treatment was shown to changed the natural history of the disease," said Dr. Djulbegovic.

In recent years however, the use of AZA-C and decitabine in the treatment of patients with MDS has been a major focus of clinical research. Although they have been shown to improve haematopoiesis in these patients, data for overall survival (OS) and event-free survival (EFS) have been inconsistent across trials.

As a direct comparative trial of AZA-C versus decitabine is still lacking, this systematic review of randomised controlled trials (RCTs) was carried out to compare the efficacy and toxicity of these 2 agents versus BSC in patients with MDS. Furthermore, the data also allowed an indirect comparison between AZA-C and decitabine.

Searches of MEDLINE, EMBASE, the Cochrane database, and meeting abstracts identified 4 relevant phase 3 RCTs, 2 comparing AZA-C with BSC, and 2 comparing decitabine and BSC. The outcomes assessed were OS, EFS, overall response rate (ORR), and TRM.

The 4 trials provided 952 patients with MDS (median age, ~70 years). When these were pooled according to hypomethylating agents versus BSC, there were significant benefits seen for the use of the hypomethylating agents for OS (hazard ratio [HR] = 0.82; 95% confidence interval [CI], 0.70-0.95), EFS (HR = 0.63; 95% CI, 0.53-0.75), and ORR (relative risk [RR], 0.79; 95% CI, 0.75-0.83), with no significant differences in TRM.

With the comparisons of each agent versus BSC individually, AZA-C showed significant benefits for both OS (HR = 0.62; 95% CI, 0.48-0.78) and EFS (HR = 0.58, 95% CI, 0.44-0.76), while decitabine saw significant benefit for EFS (HR = 0.67; 95% CI, 0.53-0.86) and ORR (RR, 0.82; 95% CI, 0.77-0.97). There was no significant difference for TRM.

Finally, as Dr. Djulbegovic noted, the indirect comparison of AZA-C and decitabine showed significantly better OS for AZA-C (HR = 0.63; 95% CI, 0.46-0.85), again with no differences for TRM.

Funding for this study was provided by Celgene.

[Presentation title: The Impact of Azacitidine and Decitabine (Hypomethylating Agents) in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis. Abstract 0661]

E-Mail this DGDispatch to a colleague

To print, use this version