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Azacitidine and Decitabine Garner Comparable Clinical Outcomes Among Older, Unfit Patients With AML

July 25, 2022

August 2022

Treatment responses and survival outcomes were comparable among older, unfit patients with acute myeloid leukemia (AML) who received either of two hypomethylating agents (HMAs), azacitidine or decitabine, according to research findings published in Blood.

“Our analysis establishes that either HMA could be used as monotherapy or in combination with venetoclax, with similar expectations for efficacy and safety between azacitidine and decitabine, including among TP53-mutated patients,” said corresponding author Amer M. Zeidan, MBBS, of Yale University.

Dr. Zeidan noted that his colleagues who manage older or unfit patients with AML often ask whether to use azacitidine or decitabine as monotherapies or in combination with venetoclax, highlighting a critical knowledge gap within the clinician community.

“The two HMAs have not been directly compared in large, randomized, prospective trials and such studies are highly unlikely to be ever conducted,” he said. “Therefore, our analysis fills an important data gap with the best possible approach, short of having a dedicated large, randomized trial.”

The study findings were based on an analysis of the phase III ASTRAL-1 trial, which enrolled 815 unfit or older patients with newly diagnosed AML across 144 sites and 24 countries. Physicians of enrolled patients preselected either azacitidine, decitabine, or low-dose cytarabine before patients were randomized to either guadecitabine or the preselected treatment choice of azacitidine or decitabine. In total, 171 patients received azacitidine and 167 patients received decitabine.

Chosen treatments were administered in 28-day cycles, which continued until the occurrence of either disease progression or unacceptable toxicity. Azacitidine was intravenously (IV) or subcutaneously administered at 75 mg/m2/day on days one through seven, while IV decitabine was administered at 20 mg/m2/day on days one through five.

The median age in both treatment groups was 76 years. Approximately 47% of patients in the azacitidine arm and 54% of patients in the decitabine arm had an Eastern Cooperative Oncology Group Performance Status of 2-3. Patients in the azacitidine and decitabine arms underwent a median of six and five treatment cycles, respectively.

Primary endpoints of the analysis were the rates of complete response (CR) and overall survival (OS). The investigators found no significant difference between the azacitidine and decitabine arms in terms of the CR rate (17.5% vs. 19.2%, respectively; p=0.78). Both groups also had similar median OS rates (8.7 months vs. 8.2 months; hazard ratio [HR] for death = 0.97). The researchers noted that these OS rates “are comparable to previous reports from phase III trials and contemporary real-world analyses.”

In a subgroup of patients with TP53 mutations who received azacitidine (n=20) or decitabine (n=19), the investigators also found no statistically significant difference in OS rates.

The most common grade 3 or higher adverse events (AEs) were hematologic and infectious in nature. No difference was found between azacitidine- and decitabine-treated patients in terms of these safety events. The azacitidine group, however, had more frequent serious AEs that led to death (38% vs. 26%; p=0.02). The 30- and 60-day all-cause mortality rates were 12% and 21%, respectively, in the azacitidine arm and 8% and 13% in the decitabine group.

Given that patients in the study were not randomized to receive azacitidine or decitabine, the study is considered an “indirect comparison” of the agents. Likewise, the study “was not specifically designed to detect statistically significant differences between” each therapy, the researchers wrote.

Despite these limitations, the researchers noted the findings still “have important implications for both clinicians and patients and support the use of azacitidine and decitabine as equivalent options potentially including combinations with novel therapies.”

Any conflicts of interest declared by the authors can be found in the original article.


Zeidan AM, Fenaux P, Gobbi M, et al. Prospective comparison of outcomes with azacitidine and decitabine in AML patients ineligible for intensive chemotherapy [published online ahead of print, 2022 May 4]. Blood. doi: 10.1182/blood.2022015832.


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