Safety Profile of Oral Azacitadine Remains Consistent in Lower-Risk MDS


The safety profile of oral azacitadine was shown to be similar across the 200-mg and 300-mg arms in patients with lower- to intermediate-risk MDS.

The safety profile of oral azacitadine was shown to be similar across the 200-mg and 300-mg arms in patients with lower- to intermediate-risk MDS.

The safety profile of oral azacitadine was shown to be similar across the 200-mg and 300-mg arms in patients with lower- to intermediate-risk MDS.

The safety of oral azacitidine (Onureg) following a decreased dosing schedule remained consistent with the previously known safety profile of the agent in lower-/intermediate-risk myelodysplastic syndrome (MDS), according to findings from the phase 2/3 ASTREON trial (NCT05469737) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“We showed that the safety profile of oral azacitidine in both 200 mg or 300 mg is identical or similar to our prior experience in other trials, such as the phase 3 AZA-MDS-003 trial [NCT01566695],” study author Guillermo Garcia-Manero, MD, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, said during a presentation of the data.

The primary end points in the trial were adverse effects (AEs) and complete remission (CR) within 6 cycles per International Working Group (IWG) 2006 criteria.

Regarding AEs, patients in both treatment arms experienced similar rates. Twenty-three patients (96%) in the 200-mg arm and 20 patients (87%) in the 300-mg arm reported having at least 1 treatment-related treatment-emergent AE (TEAE).

The most common treatment-related AEs patients experienced in either group were hematologic- and gastrointestinal-related.

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

Serious TRAEs occurred in 1 patient from the 200-mg arm and 3 patients from the 300-mg arm, researchers noted. There were 2 deaths that occurred in the 300-mg arm, which were treatment-related and treatment-emergent, respectively. No patients from the 200-mg arm experienced grade 5 AEs.

Of note, the rates of TRAEs of all grades leading to treatment discontinuation or dose reduction were higher in the 300-mg arm. Four patients (17%) in the 200-mg arm, Garcia-Manero said, discontinued treatment due to disease progression. Three patients (13%) in the 300-mg arm discontinued treatment due to TRAEs.

Regarding the co-primary end point, Garcia-Manero noted that none of the patients achieved a CR in either arm.

Secondary end points were achievement of overall response rate (ORR)–which included complete response (CR), partial remission, marrow CR, hematologic improvement-erythroid response (HI-E), HI-platelet (HI-P) response, and HI-neutrophil (HI-N) response per IWG 2006 criteria–as well as best OR and OR duration.

There were 6 patients from both dose arms that achieved HI-E; 0 patients in the 200-mg arm and 1 patient in the 300-mg arm achieved HI-P; and 1 patient in each dose group achieved HI-N.

Of note, HI rates within 6 cycles were calculated by investigator assessment per IWG 2006 criteria. This was calculated for patients who received at least 75% of the dose from cycle 1 and had at least 1 post-baseline efficacy assessment, which was the modified intent-to-treat (mITT) population.

In the mITT population, 8 of 22 patients in the 200-mg arm achieved any HI and 7 of 21 patients in the 300-mg arm achieved any HI.

The Phase 2/3 Trial

In the trial, 47 patients with lower-/intermediate-risk MDS were randomly assigned 1:1. The study evaluated safety and efficacy of oral azacitadine with best supportive care (BSC) in this patient population. Patients were assigned to 2 arms to receive at least 1 dose of oral azacitadine at either 200 mg (n = 24) or 300 milligrams (n = 23) for 14 days per a 28-day cycle plus BSC. Eligible patients were at least 18 years old and had at least 1 cytopenia.

The phase 2 portion of the trial was an open-label, dose optimization trial to help determine the recommended phase 3 dose of oral azacitadine. Most patients (89.4%) had previously received treatment for MDS, which included but was not limited to, erythropoiesis-stimulating agents, luspatercept (Reblozyl), lenalidomide (Revlimid), and imetelstat.


Garcia-Manero G, Yee K, Hernandez F, et al. Preliminary safety and efficacy of oral azacitidine (Oral-AZA) in patients (pts) with low-/Intermediate (Int)-risk myelodysplastic syndromes (MDS): Phase 2 results from the ASTREON trial. J Clin Oncol. 2024;42(suppl 16):6509. doi:10.1200/JCO.2024.42.16_suppl.6509

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