EORTC-06011: Low-Dose Decitabine versus Best Supportive Care for Elderly Patients with Intermediate- or High-Risk MDS
Slides from the journal article and transcribed comments from recent interviews with
Gail J Roboz, MD (10/6/09), Steven D Gore, MD (10/8/09) and Hagop M Kantarjian, MD (10/17/09) below
Presentation discussed in this issue:
WijerMans P et al. Low dose decitabine versus best supportive care in elderly patients with intermediate or high risk MDS not eligible for intensive chemotherapy: Final results of the randomized phase III study (06011) of the EORTC Leukemia and German MDS Study Groups. Blood 2008;Abstract 226.
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GAIL J ROBOZ, MD: This Phase III study showed a lack of survival benefit with low-dose decitabine over best supportive care, although it should be pointed out that the majority of patients did not receive multiple cycles of decitabine as received in the study with azacitidine. This highlights the need for repeated cycles over a longer period of time with the use of hypomethylating agents, in order to obtain the full benefit.
STEVEN D GORE, MD: This is a randomized trial that is similar to the azacitidine-001 study, but with decitabine versus best supportive care, in elderly patients with intermediate- or high-risk MDS. The FDA-approved treatment schedule for decitabine used in this study did not show a significant improvement in time to AML or death. I believe that these results, together with those from the AZA-001 study, establish the FDA-approved dose schedule of azacitidine as being the preferred treatment for patients with high-risk MDS. This is also acknowledged in the NCCN guidelines.
HAGOP M KANTARJIAN, MD: This study with decitabine was similar to the one with azacitidine versus conventional care. It has not been well publicized because the data were negative. In this study there were 233 patients with a median age of 70 years with the worst of the worst — patients with intermediate-2 and high-risk MDS. These patients were exposed to a dose schedule of three instead of seven days and courses were administered every six to eight weeks instead of every four weeks, with a maximum number of eight courses. I believe that with an adverse-risk population, shorter and less frequent drug exposure and a shorter number of courses, it is not unusual that a survival benefit was not seen. Notice also that in the supportive care arm, the median survival was 8.5 months in contrast to 15 months in a previous study, suggesting that this is a population that is much worse than the one in the study of azacitidine versus conventional care.
Patients received a median of four cycles of decitabine, as opposed to the median number of nine cycles administered to patients in the study with azacitidine. Consequently, the CR rate is lower and the overall response rate is lower — in the range of 34 percent. There was significant prolongation of the progression-free survival, but the bottom line is there was no survival benefit, unlike with azacitidine.
Dr Roboz is Associate Professor of Medicine and Director of the Leukemia Program at Weill Medical College of Cornell University at NewYork-Presbyterian Hospital in New York, New York.
Dr Gore is Professor of Oncology at Johns Hopkins University in Baltimore, Maryland.
Dr Kantarjian is Chairman and Professor of the Leukemia Department at The University of Texas MD Anderson Cancer Center in Houston, Texas.