The hypomethylating agents azacitidine (AZA) and decitabine (DEC) are approved in Europe for patients who are ineligible for intensive chemotherapy (IC) or hematopoietic cell transplant, but limited data are available on comparative outcomes associated with these individual agents. This study examined the efficacy and safety of AZA versus DEC in ASTRAL-1, the largest randomized trial for patients with treatment-naïve acute myeloid leukemia (TN-AML) who were not eligible for IC.
A total of 815 patients with TN-AML who were ineligible for IC were enrolled in ASTRAL-1, a global, prospective, randomized, controlled phase 3 trial. Patients were randomized 1:1 to either the DNA methyltransferase inhibitor guadecitabine (subcutaneous [SC], 60 mg/m2 on days 1-5) or a preselected treatment choice (TC) of AZA (intravenous [IV] or SC, 75 mg/m2 on days 1-7), DEC (IV, 20 mg/m2 on days 1-5), or low-dose cytarabine (SC, 20 mg twice daily on days 1-10). The co-primary end points were rates of hematologic complete response (CR) and overall survival (OS).
Of 407 patients randomized to TC, 83% (N = 338) were treated with either AZA (N = 171) or DEC (N = 167). The AZA and DEC treatment groups were well matched, with a median age of 76 years in both arms. The following baseline characteristics were observed in the AZA and DEC groups, respectively: poor performance status 2 to 3: 47.4% versus 53.9%; poor risk cytogenetics: 38% versus 33.5%; secondary AML: 38% versus 36.5%; bone marrow blasts >30%: 63.7% versus 71.3%; and presence of TP53 mutations: 12.9% versus 11.3%. The median follow-up was 25.5 months, and the median number of treatment cycles was 6 and 5 for AZA and DEC, respectively.
The CR rate was 17.5% versus 19.2% (P = .70) for AZA versus DEC, respectively, whereas the overall CR (CR + CR with incomplete platelet recovery + CR with incomplete hematologic recovery) was 22.2% versus 25.1% (P = .53) for AZA versus DEC, respectively. The median OS was 8.7 months for AZA and 8.2 months for DEC (hazard ratio, 0.97; 95% confidence interval, 0.77-1.23; log rank P = .8).
The rates of grade ≥3 adverse events (AEs; 88.9% vs 87.4%), serious AEs (81.9% vs 76.0%), and 30-day all-cause mortality (11.7% vs 7.8%) were not significantly different between AZA and DEC, respectively. Although not statistically significant, 60-day, all-cause mortality was numerically higher with AZA (20.5%) versus DEC (13.2%; P = .07).
In this large study comparing clinical outcomes with AZA and DEC for patients with TN-AML not eligible for IC, no significant differences in CR, overall CR, OS, or safety were observed.
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: 25th European Hematology Association Congress Virtual; June 11-21, 2020. Abstract S142.