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An analysis of the phase 3 ASTRAL-2 trial did not show an overall survival (OS) benefit with guadecitabine in patients with relapsed/refractory acute myeloid leukemia (AML), but possible benefits were seen for some subgroups. This is according to results presented in a poster at the 2021 American Society of Hematology (ASH) Annual Meeting by Gail Roboz, MD, from Weill Cornell Medicine and New York Presbyterian Hospital in New York, New York, and colleagues.
The study evaluated the next-generation hypomethylating agent guadecitabine in comparison to treatment choice following intensive anthracycline-based induction in patients with relapsed/refractory AML. The primary endpoint was OS, and secondary endpoints included 12- and 24-month survival, complete response (CR), event-free survival, and safety.
Treatment choice included low-intensity treatment, high-intensity treatment, or best supportive care. Low-intensity therapy involved low-dose cytarabine, decitabine, or azacitidine. High-intensity therapy choices were high-dose cytarabine; mitoxantrone, etoposide, and cytarabine; or fludarabine, cytarabine, granulocyte colony-stimulating factor with or without idarubicin.
The median study follow-up was 21.6 months, and the median number of cycles was 3.0 with guadecitabine and 2.0 with treatment choice. A total of 148 patients were randomized to the guadecitabine arm, with 154 patients in the treatment choice arm.
The median OS was 6.4 months with guadecitabine, and it was 5.4 months with treatment choice, a nonsignificant difference (hazard ratio, 0.88; 95% CI, 0.67-1.14; P =.3). The 12-month survival rates were 32% with guadecitabine and 26% with treatment choice; 24-month survival rates were 19% with guadecitabine and 10% with treatment choice.
Various subgroups showed better OS with guadecitabine. These included younger and fitter patients, patients with refractory AML, those with a lower disease burden of ≤30% peripheral blood blasts, and patients who received adequate therapy involving 4 or more cycles.
CR rates were 12.8% with guadecitabine and 7.1% with treatment choice (P =.051), while rates of CR with partial hematologic recovery were 16.9% with guadecitabine and 7.8% with treatment choice (P =.007). Overall composite CR rates, including CR and CR with incomplete hematologic recovery, were 27% with guadecitabine and 14.3% with treatment choice (P =.003).
Grade 3 or higher adverse events were seen in 89% of patients in the guadecitabine arm and in 84.4% of those in the treatment choice arm. Safety profiles were similar between arms, except that grade 3 or higher neutropenia was reportedly more frequent with guadecitabine (P =.003).
Dr Roboz and colleagues concluded that there was not a significant OS benefit in this study but that some prospective subgroups did see a benefit. “Patients who got an adequate number of cycles, regardless of the treatment assignment, did significantly better on guadecitabine, which was similar to the ASTRAL-1 study results in treatment-naive patients who could not get intensive chemotherapy,” Dr Roboz also noted in a presentation accompanying the research team’s poster.
“The secondary endpoints favored guadecitabine, and the safety profile was consistent with the expected safety profile of treatment in the study population, with no clinically significant differences between the treatment arms,” Dr Roboz said in her presentation.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Roboz GJ, Sanz G, Griffiths EA, et al. Results from a global randomized phase 3 study of guadecitabine (G) vs treatment choice (TC) in 302 patients with relapsed or refractory (r/r) acute myeloid leukemia after intensive chemotherapy (ASTRAL-2 Study). Presented at ASH 2021; December 11 to 14, 2021. Abstract 2344.
This article originally appeared on Hematology Advisor