Phase 2 Results From the ASTREON Trial: Preliminary Safety and Efficacy of Oral AZA in Patients With Low-/Intermediate-Risk MDS

Unmet need remains for new treatment options in lower-risk myelodysplastic syndromes (MDS), aiming to address cytopenia and hinder the progression to higher-risk MDS and acute myeloid leukemia. This report highlights the safety and preliminary efficacy data obtained from phase 2 of the ASTREON study, which investigated the effects of 14-day oral azacitidine (AZA) regimens in patients with low-/intermediate-risk MDS.

The ASTREON study is a phase 2/3 multicenter trial designed to evaluate the safety and efficacy of oral AZA in combination with best supportive care (BSC) for patients with low-/intermediate-risk MDS. The phase 2 portion of the trial is an open-label dose optimization study to determine the recommended phase 3 dose of oral AZA.

Eligible patients, aged ≥18 years, with Revised International Prognostic Scoring System low-/intermediate-risk MDS, and ≥1 cytopenias, were randomized 1:1 to receive either 200 mg or 300 mg of oral AZA daily for 14 days in a 28-day cycle, along with BSC.

The study’s primary endpoints included adverse event (AE) rates and complete remission rates within 6 cycles according to the International Working Group (IWG) 2006 criteria. Secondary endpoints encompass overall response (OR) rates (including complete response, partial remission, marrow complete response, hematologic improvement-erythroid [HI-E] response, hematologic improvement [HI]-platelet response, and HI-neutrophil response, per IWG 2006 criteria), best OR, and OR duration.

Forty-seven patients were randomly assigned and administered ≥1 doses of oral AZA (200 mg, n=24; 300 mg, n=23). In the 200-mg and 300-mg groups, 8 and 6 patients discontinued treatment, respectively. The median durations of treatment were 31.6 (range, 12.1-42.3) weeks and 32.7 (range, 7.7-47.3) weeks for the 200-mg and 300-mg groups, respectively. The rates of AEs were comparable between the groups.

The most frequent AEs related to treatment in both groups were hematologic and gastrointestinal. Treatment-related serious AEs were reported in 1 of 24 patients in the 200-mg arm and 3 of 23 in the 300-mg arm. In total, ∼33.3 of the patients in each group achieved any HI. Six patients in each dose group achieved HI-E.

The safety profile of oral AZA 200 mg and 300 mg remained consistent with the established safety standards. Initial efficacy data indicate the need for further assessment of oral AZA in lower-risk MDS.

Source: Garcia-Manero G, Yee KWL, 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. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; abstract 6509.