MILAN — In older patients with newly diagnosed acute myeloid leukemia (AML), azacitidine (Vidaza, Celgene) is associated with significantly better overall and 1-year survival than conventional treatment regimens, according to a multicenter phase 3 randomized trial.
"These findings represent the largest overall survival and 1-year survival benefits seen with a low-intensity therapy in elderly patients with acute myeloid leukemia," said Hervé Dombret, MD, from Hôpital Saint Louis in Paris.
He presented the late-breaking findings here at the19th Congress of the European Hematology Association.
Prognosis is poor for older patients with AML, many of whom are not suited to intensive chemotherapy because of its high toxicity. Studies have shown a median overall survival of 2 to 8 months, depending on comorbidities and biologic risk factors, Dr. Dombret reported.
However, a previous study showed that azacitidine improved overall survival in older AML patients with low bone marrow, compared with conventional treatment (J Clin Oncol. 2010;28:562-569).
In their multicenter open-label trial, Dr. Dombret and colleagues assessed the effect of azacitidine on overall survival and safety.
All patients were newly diagnosed with de novo or secondary AML, were not eligible for allogeneic stem cell transplantation, and had blasts counts above 30%. Median age of the cohort was 75 years, and 59% was male.
Investigators chose the most appropriate of 3 conventional therapies for each patient: standard intensive chemotherapy; subcutaneous low-dose cytarabine (20 mg/m² per day for 10 days of every 28-day cycle); or best supportive care. Baseline characteristics were similar in all groups.
Of the 488 study participants, about half were randomized to also receive subcutaneous azacitidine 75 mg/m² per day for 7 days of every 28-day cycle.
Median overall survival was better with azacitidine than without, but the difference was not significant (10.4 vs 6.5 months; P = 1.0 stratified).
However, on sensitivity analysis, median overall survival was significantly better with azacitidine (12.1 vs 6.9 months; P = .01).
There was a significant 12.3% difference in 1-year survival rates between the azacitidine and no-azacitidine groups. However, there were no differences in 30- or 60-day mortality between the 2 groups.
Hematologic adverse events were generally higher in the azacitidine group than in the no-azacitidine group, including grade 3/4 anemia (16% vs 5%), neutropenia (26% vs 5%), and thrombocytopenia (24% vs 5%). Febrile neutropenia rates were the same in the 2 groups (28% vs 28%).
Despite falling short of statistical significance for the primary end point of overall survival, the benefits of azacitidine for older ALM patients are clear, Dr. Dombret said.
"Overall survival with censoring at subsequent AML therapy demonstrated a statistically significant benefit for azacitidine compared with conventional care," he said. In addition, "the safely profile was consistent with that previously observed with azacitidine."
"I am not convinced," said Richard F. Schlenk, MD, chief physician and head of the AMLSG Study Centre at the UniversityofUlm in Germany.
He expressed skepticism about the findings because of the lack of data on the molecular genetics of patients, which is considered essential for ALM research.
"For statistical planning to be performed before a trial starts, it is absolutely necessary to avoid false-positive results," he said.
"There is no subgroup analysis on molecular subsets because the company has not put biobanking into place," he told Medscape Medical News. "This has been a major mistake."
Another drug, decitabine, has been approved for AML in Europe, Dr. Schlenk noted. However, it was not approved by the US Food and Drug Administration for AML because of an unfavorable risk/benefit profile, as reported by Medscape Medical News.
The study was supported by Celgene. Dr. Dombret has received honoraria from Celgene.
19th Congress of the European Hematology Association (EHA): Abstract LB-6212. Presented June 14, 2014.
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Cite this: Azacitidine Effective in Elderly With Newly Diagnosed AML - Medscape - Jun 18, 2014.