The US Food and Drug Administration (FDA) has approved an oral form of azacitidine (Onureg) for use as maintenance therapy for patients with acute myeloid leukemia (AML) who have achieved a first complete remission.

The approval extends to patients who have achieved complete remission with incomplete blood count recovery following intensive induction chemotherapy and who are unable to complete intensive curative therapy.

The approval was based on data from the QUAZAR AML-001 trial, which showed that oral azacitadine significantly improved overall survival when compared to placebo.

"It's not too hard to get these patients into remission," Harry P. Erba, MD, PhD, director of the Leukemia Program at the Duke Cancer Institute, Durham, North Carolina, told Medscape Medical News last year, when these results were first presented at the 2019 annual meeting of the American Society of Hematology. "The problem comes in keeping them in remission."

Despite various attempts, there has been no success over the past 30 years in defining maintenance treatment for these patients, Andrew H. Wei, MBBS, PhD, from the Alfred Hospital in Melbourne, Australia, said.

"Oral azacitidine represents a new therapeutic standard for patients with AML in remission," he said.

Azacitidine is a hypomethylating agent that incorporates into DNA and RNA. It has long been used as an injectable therapy for the treatment of myelodysplastic syndromes.

The approval of the new oral formulation for the new indication of AML "is the culmination of over a decade of research and 13 preclinical and clinical trials," said Giovanni Caforio, M.D., chairman and chief executive officer of Bristol-Myers Squibb, in a statement.

The QUAZAR AML-001 trial was a phase 3, international study involving 472 patients with AML who were within achieving a first complete remission or remission with incomplete blood recovery. All patients has received intensive induction chemotherapy with or without consolidation treatment, per investigator preference prior to study entry, and were not candidates for hematopoietic stem cell transplant at the time of screening.

Patients were randomly assigned to receive either oral azacitidine 200 mg daily on days 1 to 14 of a repeat 28-day cycle (n = 278) or matching placebo (n = 274). Treatment was continued indefinitely until blast count was more than 15% or patients experienced unacceptable toxicity or underwent transplant.

At a median follow-up of over 41.2 months, the median overall survival was significantly longer for patients who received oral azacytidine, at 24.7 monthsvs 14.8 months for those who received placebo (P < .0009; hazard ratio [HR], 0.69).

Relapse-free survival was also significantly prolonged to 10.2 months for patients who received oral azacitidinevs 4.8 months for those who received placebo (HR, 0.65; P < .0001).

Serious adverse reactions occurred in 15% of patients who received azacytidine. Events that occurred in 2% of patients include pneumonia (8%) and febrile neutropenia (7%). There was one fatal event.

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

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FDA Approves First Maintenance Therapy for AML - Medscape