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Similar safety and efficacy of azacitidine and decitabine in patients with treatment-naïve acute myeloid leukaemia who are ineligible for intensive chemotherapy

The ASTRAL-1 trial represents the largest comparison of clinical outcomes associated with azacitidine and decitabine in patients with treatment-naïve acute myeloid leukaemia (AML) who are unable to undergo intensive chemotherapy. Despite the fact that patients in this trial were randomised between guadecitabine and a preselected treatment choice of decitabine, azacitidine or low dose Ara-C, with no direct randomisation of azacitidine versus decitabine, the patients’ characteristics were well balanced between both treatment arms. There were no significant differences in complete response, overall complete response, overall survival or safety between azacitidine and decitabine.


Older patients (≥65 years of age) with treatment-naïve (TN) AML who are ineligible for intensive chemotherapy have limited therapeutic options and face a poor outcome. The hypomethylating agents azacitidine and decitabine have been the standard-of-care for these patients for more than a decade. To date, data of a direct comparison of the efficacy and safety of azacitidine and decitabine in a prospective large randomised study are lacking. Zeidan et al. took advantage of the largest randomised trial for patients with TN AML who were not eligible for intensive chemotherapy, ASTRAL-1, to compare efficacy and safety of azacitidine versus decitabine in patients randomised to these two treatments.

The phase III ASTRAL-1 trial enrolled patients with TN AML who were ineligible for intensive chemotherapy using stringent criteria including age ≥75 year, the presence of comorbidities, or an ECOG performance status of 2-3. Patients were randomly assigned (1:1) to either guadecitabine, a next generation hypomethylating agent (60 mg/m2/day subcutaneously on days 1 to 5) or a preselected treatment choice of azacitidine (75 mg/m2/day intravenously or subcutaneously on days 1 to 7), decitabine (20 mg/m2/day intravenously on days 1 to 5), or low dose Ara-C (LDAC) (20 mg subcutaneously, twice daily on days 1-10). AML diagnosis and responses were assessed by an independent central pathologist blinded to randomisation assignment and responses were recorded using IWG 2003 criteria.


A total number of 815 patients were randomised to guadecitabine or treatment choice. Of the 407 patients randomised to treatment choice, 338 (83%) were treated with either azacitidine (171 patients) or decitabine (167 patients). Baseline variables were well balanced between azacitidine and decitabine patients without any significant differences in baseline characteristics. After a median follow up of 25.5 months, the median number of treatment cycles was 6 for azacitidine and 5 for decitabine. A complete response (CR) was obtained in 17.5% of the patients in the azacitidine arm and in 19.2% of the patients in the decitabine arm (p= 0.78) with an overall CR (CR+CRp+CRi) of 22.2% and 25.1%, respectively. The median overall survival (OS) was highly comparable for both agents with a median OS of 8.7 months in the azacitidine arm and 8.2 months with decitabine (HR [95% CI]: 0.97 [0.77-123], p=0.81). One- and two-year survival rates in the azacitidine arm were 39% and 15%, respectively, as compared to 32% and 14% in the decitabine arm. Additional subgroup analyses by baseline characteristics and molecular genetic mutations also failed to detect any difference between azacitidine and decitabine in any subgroup.

The most common grade ≥3 adverse events (AEs) were febrile neutropenia (29% versus 26% in the azacitidine and decitabine arms, respectively), pneumonia (23% versus 19%), thrombocytopenia (18% versus 23%), neutropenia (16% versus 25%, p= 0.06), anaemia (16% versus 19%) and sepsis (14% versus 12%). There was a significantly higher incidence of serious AEs (p=0.02) leading to death in the azacitidine arm (38%) as compared to the decitabine arm (26%) with a trend (p=0.08) of higher 60-day all-cause mortality on azacitidine (21%) versus decitabine (13%).


The ASTRAL-1 trial is the largest comparative dataset of azacitidine versus decitabine in TN AML patients who are ineligible for intensive chemotherapy. No differences in complete response, composite complete response or survival in the overall population or all major clinical and genetic subgroups were detected. There were also no major safety differences although the rate of fatal serious adverse events and the early 60-day mortality trended to be higher with azacitidine.


Zeidan AM, Fenaux P, Gobbi M, et al. Comparative results of azacitidine and decitabine from a large prospective phase 3 study in treatment naïve acute myeloid leukemia (TN-AML) not eligible for intensive chemotherapy. Presented at EHA 2020; Abstract S142.

Speaker Amer Zeidan

Amer Zeidan

Amer Zeidan, MBBS, MHS, Yale University and Yale Cancer Center, New Haven, United States


See: Keyslides


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