QUAZAR trial, Aza maintenance

Background

Phase III RCT (n=472), intermediate/poor-risk de novo or secondary AML (prior MDS/CMML) achieving first CR/CRi after intensive chemotherapy, ≥55 years and HSCT-ineligible. Excluded CNS disease, good-risk cytogenetics, prior hypomethylating agents, prior CML/MPN.

Interventions and follow up

Arm A: Oral azacitidine (CC-486) 300 mg daily days 1-14, Q28D until progression
Arm B: Placebo
Primary endpoint: OS
Median follow-up: 41.2 mo

Results

mOS: 24.7 vs 14.8 mo (A vs B), P<.001
mRFS: 10.2 vs 4.8 mo (A vs B), P<.001

Adverse events

Hematologic/cytopenias (grade ≥3): Neutropenia 41% vs 24%; thrombocytopenia 22% vs 22%; anemia 14% vs 13%. Any grade ≥3 event 72% vs 63%.
GI (grade 1-2, common): Nausea 65% vs 24%; vomiting 60% vs 10%; diarrhea 50% vs 21%.
Discontinuation for AEs: 13% vs 4%.

Conclusions

Oral azacitidine maintenance significantly prolonged OS and RFS in older HSCT-ineligible AML patients in first remission after intensive chemotherapy.

Key Limitations

Restricted to HSCT-ineligible patients in CR/CRi after intensive chemo; not applicable to transplant candidates or those treated with non-intensive frontline regimens. GI toxicity limited adherence in some patients. Oral CC-486 is not bioequivalent to injectable azacitidine.

Clinical Context

FDA (2020) and EMA-approved oral azacitidine (Onureg) for AML maintenance in first remission after intensive induction in patients unable to complete curative therapy. ELN/ASCO frameworks incorporate it as standard maintenance for this population.
*CR: <5% marrow blasts, no Auer rods, no extramedullary disease, transfusion-independent, ANC >1.0 × 10⁹/L, platelets ≥100 × 10⁹/L. CRi: as above but ANC <1.0 or platelets <100 × 10⁹/L.

References