Safety Profile of Lower-Dose Oral Onureg Remains Consistent in Lower-Risk MDS


The safety profile of 200 milligrams and 300 milligrams of oral Ongureg were similar in patients with lower- to intermediate-risk MDS.

The safety of oral Onureg (azacitidine) following a decreased dosing schedule remained consistent with the previously known safety profile of the drug in patients with lower- or intermediate-risk myelodysplastic syndromes (MDS), according to data from a phase 2/3 trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“We showed that the safety profile of oral [Onureg] in both 200 or 300 milligrams is identical or similar to our prior experience in other trials, such as the AZA-MDS-003 trial,” Dr. Guillermo Garcia-Manero, department of leukemia, division of cancer medicine at The University of Texas MD Anderson Cancer Center, said during a presentation of the data.

Study Highlights:

  • The safety of oral Onureg (azacitidine) was consistent with what was already known about the safety of the drug in patients with low- or intermediate-risk MDS.
  • Most (89.4%) of the patients in the trial had already been treated for MDS with other medications.
  • No one in the trial achieved complete remission, but side effects were common. Some of these side effects were severe.

In the ASTREON trial, 47 patients with low- or intermediate-risk MDS were evenly divided among two groups. Patients either received at least one oral dose of Onureg of either 200 milligrams (24 patients) or 300 milligrams (23 patients).

Eligible patients were at least 18 years old and experienced at least one cytopenia, a condition when patients have lower-than-normal levels of blood cells, according to the National Cancer Institute. This included conditions such as anemia, thrombocytopenia (lower levels of platelets) or neutropenia (lower levels of white blood cells called neutrophils).

The purpose of the phase 2 portion of the trial was to evaluate the safety and how effective treatment is. This helped determine the appropriate dose of treatment for patients in phase 3. The majority of patients (89.4%) had previously received treatment for MDS, which included but was not limited to erythropoiesis (red blood cell)-stimulating agents, Reblozyl (luspatercept), Revlimid (lenalidomide) and imetelstat.

Garcia-Manero noted that four patients (17%) in the 200-milligram group stopped the treatment because of disease worsening. Three patients (13%) from the 300-milligram group stopped treatment because of treatment-emergent side effects.

The main result measured at the end of the study were side effects and complete remission, meaning there is no evidence of disease (NED). However, Garcia-Manero reported that “none of the patients actually achieved a complete remission,” from either dose group in the trial.

Regarding side effects, researchers determined that patients in both treatment groups experienced similar side effect rates. Of the patients in the 200-milligram group, 23 of 24 (96%) experienced treatment-related side effects, according to the presentation. There were 20 of 23 patients (87%) in the 300-milligram group who experienced at least one treatment-related side effects.

The most common treatment-related side effects patients experienced in either group were hematologic- and gastrointestinal (GI)-related.

“The most common [treatment-related toxicities] were neutropenia followed by constipation, nausea, thrombocytopenia, basically, prototypical hematological and GI toxicity profile that we saw with this agent in the past,” Garcia-Manero explained.

Serious treatment-related side effects occurred in one patient from the 200-milligram group and three patients from the 300-milligram group, researchers noted. According to the presentation of the data, two patients died in 300-milligram group because of treatment and no patients died in the 200-milligram group.

Secondary results measured after the study included achievement of overall response (OR; percentage of patients whose cancer shrinks or disappears), best OR and how long OR occurred. Achievement of OR included complete response to treatment, partial remission and marrow CR.

Of note, achievement of OR also included hematologic improvement-erythroid response (HI-E; when treatment helps the body produce more red blood cells), HI-platelet (HI-P) response (treatment helping platelet count) and HI-neutrophil (HI-N) response (treatment helping white blood cell count), the researchers reported.

In the study, HI rates were calculated for patients who received at least 75% of the dose from the first cycle of treatment and had at least one assessment after baseline to see how effective treatment was. This group of patients was considered the modified intent-to-treat (mITT) population.

In the mITT population, seven of 23 patients (30%) from the 200-milligram group achieved any HI and seven of 21 patients (33%) in the 300-milligram group achieved any HI. Six patients in each dose group achieved HI-E. Zero patients in the 200-milligram group and one patient in the 300-milligram group achieved HI-P. One patient in each dose group achieved HI-N, the data showed.

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