Onureg Prolongs Survival in Acute Myeloid Leukemia

Maintenance therapy with Onureg, an oral formulation of the chemotherapy azacitidine, significantly prolonged overall survival (OS) and relapse-free survival compared to placebo in older patients with acute myeloid leukemia who were in remission after chemotherapy, according to findings from the QUAZAR AML-001 trial published in The New England Journal of Medicine.

Researchers can take these findings a step further and eventually find the patients who would benefit the most from this maintenance therapy.

“Determining which molecular characteristics may influence outcomes of maintenance therapy could be useful for identifying patients who are likely to derive the most benefit from this approach,” the study authors wrote. “Although assessment of molecular abnormalities was not required for this trial, correlative samples were obtained for potential future analysis.”

According to the introduction of the publication, acute myeloid leukemia is “an aggressive disease that predominantly affects older people.” Standard induction chemotherapy often leads to complete remission in 40% to 60% of patients aged 60 years and older, although most patients (80% to 90%) eventually relapse. An important treatment goal for these patients is preventing early acute myeloid leukemia relapse with therapy after remission is achieved. One option for this, hematopoietic stem-cell transplantation, can be curative, although this treatment is not possible in many older patients.

In this phase 3 trial, researchers analyzed data from 472 patients (median age, 68 years) aged 55 years or older with acute myeloid leukemia who were in remission after chemotherapy and who were not candidates for hemopoietic stem-cell transplantation. These patients were randomly assigned either Onureg (238 patients) or placebo (234 patients).

The primary end point for this trial was OS, or the time from randomization to all-cause death. Other pivotal secondary end points included health-related quality of life and relapse-free survival, defined as the time from randomization, death or relapse, whichever occurred first.

During a median follow-up of 41.2 months, patients assigned Onureg had a significantly longer median overall survival compared to those assigned placebo (24.7 months versus 14.8 months). The Onureg group also had a significantly longer relapse-free survival versus the placebo group (10.2 months versus 4.8 months). Benefits obtained with Onureg regarding relapse-free survival and OS were observed in most subgroups when defined by patient characteristics at the start of the trial.

The most common side effects in both groups were mild to moderate gastrointestinal events including vomiting, nausea and diarrhea. Common severe side effects in the Onureg and placebo groups included thrombocytopenia (low platelets in the blood; 22% and 21%, respectively) and neutropenia (very low counts of a type of white blood cells calls neutrophils; 41% and 24%, respectively).

Based on results of this trial, the Food and Drug Administration in September approved Onureg for use in this patient population.

Patients assigned Onureg had preserved overall health-related quality of life during treatment.

“Despite demonstrable survival advantages with (oral azacitidine) maintenance therapy, the risk of eventual relapse and death from (acute myeloid leukemia) remains problematic,” the study authors wrote. “Whether (oral azacitidine) may benefit patients with (acute myeloid leukemia) when it is used in other clinical contexts requires further investigation.”

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