FDA Approves Oral Azacitidine as Maintenance Therapy for Adults With AML in First Remission

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On September 1, the U.S. Food and Drug Administration (FDA) approved oral azacitidine (Onureg; also known as CC-486) for the continued treatment of adult patients with acute myeloid leukemia (AML) who achieved first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and who are not able to complete intensive curative therapy.

“Continued treatment with [oral azacitidine] demonstrated an overall survival benefit in adults with AML who had achieved first complete remission in the QUAZAR AML-001 study and, notably, it has the potential to do this in a convenient manner, given its once-daily oral formulation,” said Andrew Wei, MBBS, PhD, of the Alfred Hospital and Monash University, Melbourne, Australia. “This approval should help establish continued treatment with azacitidine as a standard component of AML therapy for adults who achieved first complete remission following chemotherapy and who cannot proceed to intensive curative therapy, like hematopoietic stem cell transplant.”


The approval is based on results from the pivotal phase III QUAZAR AML-001 study. Eligible patients were age 55 or older, had AML, were within 4 months of achieving first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy with or without consolidation treatment (per investigator preference prior to study entry), and were not candidates for hematopoietic stem cell transplant (HSCT) at the time of screening. The study enrolled 472 patients, randomly assigned 1:1 to receive either oral azacitidine at 300 mg (n = 238) or placebo (n = 234) once daily for 14 days of a 28-day cycle, plus best supportive care. The median duration of treatment was 12 cycles (range = 1–82) for patients in the oral azacitidine group and 6 cycles with placebo (range = 1–76).

Treatment with azacitidine resulted in a statistically significant and clinically meaningful improvement in overall survival (OS), the study’s primary endpoint, of nearly 10 months compared to placebo. Median OS from time of random assignment was longer than 2 years (24.7 months; 95% confidence interval [CI] = 18.7–30.5) among patients who received azacitidine compared to 14.8 months (95% CI = 11.7–17.6) among patients receiving placebo (hazard ratio [HR] = 0.69, 95% CI = 0.55–0.86, P = .0009). Treatment was continued until disease progression or unacceptable toxicity.

Adverse Events

Azacitidine has warnings and precautions for risks of substitution with other azacitidine products, myelosuppression, increased early mortality in patients with myelodysplastic syndromes, and embryo-fetal toxicity. Due to substantial differences in the pharmacokinetic parameters, azacitidine tablets should not be substituted for intravenous or subcutaneous azacitidine as it may result in a fatal adverse reaction. New or worsening grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received azacitidine tablets, respectively. Febrile neutropenia occurred in 12% of patients. Complete blood counts should be monitored, dosing should be modified as recommended, and standard supportive care should be provided if myelosuppression occurs.

Serious adverse reactions occurred in 15% of patients who received azacitidine. Serious adverse reactions occurring in ≥ 2% of patients who received oral azacitidine included pneumonia (8%) and febrile neutropenia (7%). One fatal adverse reaction (sepsis) occurred in a patient who received oral azacitidine.

The most common adverse reactions with oral azacitidine vs placebo were nausea (65% vs 24%), vomiting (60% vs 10%), diarrhea (50% vs 21%), fatigue/asthenia (44% vs 25%), constipation (39% vs 24%), pneumonia (27% vs 17%), abdominal pain (22% vs 13%) arthralgia (14% vs 10%), decreased appetite (13% vs 6%), febrile neutropenia (12% vs 8%), dizziness (11% vs 9%), and pain in extremity (11% vs 5%). Of patients who received oral azacitidine, permanent discontinuation due to an adverse reaction occurred in 8% of patients.

Results from the QUAZAR AML-001 trial were first presented at the 2019 American Society of Hematology Annual Meeting & Exposition.