Survival projections suggest that oral azacitidine may improve outcomes compared with placebo among a subset of patients with acute myeloid leukemia (AML) who are in remission, according to research presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO).
The phase 3 QUAZAR AML-001 trial (ClinicalTrials.gov Identifier: NCT01757535) was designed to evaluate the relative safety and efficacy of oral azacitidine vs placebo among patients with AML in remission after intensive chemotherapy who are ineligible for transplantation. Initial results suggested that azacitidine improves overall survival (OS) compared with placebo (median OS, 24.7 vs 14.8 months, respectively; P <.001).
At primary cut-off, however, the data suggested that OS curves converged at approximately 4 years. At this point, 26.5% of patients were still alive and researchers unblinded the study. For this presentation at SOHO 2022, the authors investigated whether OS curves differed at long-term follow-up.
Overall, 472 patients were randomly assigned to receive azacitidine (238 patients) or placebo (234 patients). All patients were at least 55 years old and had intermediate- or poor-risk cytogenetics at AML diagnosis. At the point where the study was unblinded, patients who were receiving azacitidine had the opportunity to proceed to an extension face.
Although OS did not appear to change from the initial cutoff, survival curves separated, but did not reconverge, at later time-points. The estimated 3-year OS rates in the experimental vs placebo groups were 37.4% vs 27.9%, respectively, suggesting an improvement of 9.5% (95% CI, 0.9%-18.1%).
Further analysis suggested that long-term survivors — defined as being alive at least 3 years after being randomly assigned — were more likely to have intermediate-risk cytogenetics and mutated NPM1, and less likely to have measurable residual disease at diagnosis.
The authors acknowledged that “median OS was unchanged, but at later time-points the tails of the [azacitidine] and placebo OS curves showed greater separation, indicating sustained [long-term] OS benefit.”
Ravandi F, Wei AH, Döhner H, et al. Oral Azacitidine (Oral-AZA) in patients with acute myeloid leukemia (AML) in first remission after intensive chemotherapy (IC): long-term overall survival (OS) results from the phase 3 QUAZAR AML-001 trial. Presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 28-October 1, 2022. Abstract AML-457.