US FDA approves azacitidine oral pills for treating AML

US FDA approves azacitidine oral pills for treating AML

Azacitidine tablets (Onureg) recently received the US FDA nod for treatment of patients with acute myeloid leukaemia (AML) who achieved first complete remission (CR) or CR with incomplete blood count recovery (CRi) after intensive induction chemotherapy and are not able to complete intensive curative therapy.

The approval was based on results from the phase 3 QUAZAR AML-001 trial that involved 472 patients with AML. The patients were randomly assigned in a 1:1 ratio to receive 300 mg of oral azacitidine (n=238) or placebo (n=234), once daily for 14 days of a 28-day cycle.

The patients, who were aged 55 years or older, had achieved first CR or CRi after intensive induction chemotherapy with or without consolidation therapy within the past four months, and were not candidates for hematopoietic cell transplantation at the time of screening.

The main efficacy outcome measure was overall survival (OS). Median OS was 24.7 months (95% CI, 18.7-30.5 months) in the oral azacitidine arm and 14.8 months (95% CI, 11.7-17.6 months) in the placebo arm (hazard ratio, 0.69; 95% CI, 0.55-0.86; P=0.0009). A subgroup analysis showed consistency in the OS benefit among patients who achieved CR and those who achieved CRi.

Oral azacitidine was permanently discontinued due to an adverse event (AE) in 8% of patients. Serious AEs occurred in 15% of patients who received oral azacitidine in the trial. New or worsening grade 3 or 4 neutropenia and thrombocytopenia occurred in 49% and 22% of patients who received oral azacitidine, respectively. Febrile neutropenia occurred in 12% of patients.

The most common AEs occurring in at least 10% patients receiving oral azacitidine were nausea, vomiting, diarrhoea, fatigue/asthenia, constipation, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness and pain in extremity.

The agency advised clinicians to monitor complete blood counts in patients receiving oral azacitidine; if myelosuppression occurs, dosing should be modified and standard supportive care provided.

Due to substantial differences in the pharmacokinetic parameters, oral azacitidine should not be substituted for IV or subcutaneous azacitidine because it may result in a fatal AE.