The FDA has now approved azacitidine tablets (Onureg®, Celgene) for the maintenance treatment of acute myeloid leukemia (AML) after intensive induction chemotherapy in patients who are unable to complete intensive curative therapy and who have achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi).
The approval was based on data from the multicenter, double-blind phase 3 QUAZAR trial (NCT01757535), in which 472 patients with AML who achieved CR or CRi with intensive induction chemotherapy, with or without subsequent consolidation therapy, were randomized in a 1:1 ratio to receive 300 mg oral azacitidine or placebo on days 1 to 14 of each 28-day cycle for a primary efficacy end point of overall survival.
Oral azacitidine increased median overall survival compared with placebo (24.7 vs 14.8 months), with consistency in survival benefit regardless of whether patients had achieved CR or CRi.
"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," commented study investigator Andrew Wei, MBBS, PhD, Head of Leukemia Research at the Alfred Hospital, Melbourne, Australia, in a press release. "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."
In the study, health-related quality of life was maintained at comparable rates between oral azacitidine and placebo. Oral azacitidine was generally well tolerated in all age groups, including in patients aged 75 years or older. Any-grade adverse events occurring in at least 10% of patients treated with oral azacitidine included nausea, vomiting, diarrhea, fatigue/asthenia, constipation, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, and pain in the extremities.
The recommended dosage is 300 mg once daily, taken with or without food, on Days 1 through 14 of each 28-day cycle until disease progression or unacceptable toxicity.
For More Information
Clinicaltrials.gov (2019). Efficacy of oral azacitidine plus best supportive care as maintenance therapy in subjects with acute myeloid leukemia in complete remission (QUAZAR AML-001). NLM identifier: NCT01757535.
Roboz GR, Dohner H, Pocock C, et al (2020). Health-related quality of life (HRQoL) in the phase III QUAZAR-AML-001 trial of CC-486 as maintenance therapy for patients with acute myeloid leukemia (AML) in first remission following induction chemotherapy (IC). J Clin Oncol (ASCO Virtual Scientific Program Abstracts), 38(suppl_15). Abstract 7533. DOI:10.1200/JCO.2020.38.15_suppl.7533
Ravandi F, Wei A, Dohner H, et al (2020). CC-486 is safe and well-tolerated as maintenance therapy in elderly patients (≥75 years) with acute myeloid leukemia (AML) in first remission following induction chemotherapy: results from the phase III QUAZAR AML-001 trial. J Clin Oncol (ASCO Virtual Scientific Program Abstracts), 38(suppl_15). Abstract 7530. DOI:10.1200/JCO.2020.38.15_suppl.7530
United States Food & Drug Administration (2020). FDA approves Onureg (azacitidine tablets) for acute myeloid leukemia. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-onureg-azacitidine-tablets-acute-myeloid-leukemia?utm_campaign=Onureg%20-%20azacitidine%20tablets%209-1-2020&utm_medium=email&utm_source=Eloqua&elqTrackId=48e156917e6b45cf966618381bd71caf&elq=2a1450fd6afa48968f48fc6180eea384&elqaid=14066&elqat=1&elqCampaignId=12073
Image credit: National Cancer Institute.