Phase III ASTRAL-1 Study of Guadecitabine in Patients With Treatment-Naive AML Ineligible to Receive Intensive Induction Chemotherapy

Results were recently announced from the ASTRAL-1 study evaluating the efficacy and safety of guadecitabine in adults with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive induction chemotherapy. The study did not meet its co-primary endpoints: complete response rate (P > .04) and overall survival (P > .01), as per the protocol analysis plan, compared with the control arm of physician’s choice of azacitidine, decitabine, or low-dose cytarabine.

Evaluation of the study’s secondary endpoints and safety data is ongoing. The full data will be presented at an upcoming scientific meeting.

The ongoing global phase III ASTRAL-2 and ASTRAL-3 studies evaluating guadecitabine in the treatment of relapsed or refractory AML and relapsed or refractory myelodysplastic syndromes and chronic myelomonocytic leukemia will continue.

“We are disappointed in the outcome of the ASTRAL-1 study,” said Mohammad Azab, MD, MSc, MBA, President and Chief Medical Officer of Astex. “The study used very strict criteria of ineligibility to receive intensive chemotherapy based on age (> 75 years) or poor performance status (ECOG performance status of 2 or 3) or comorbidities, which made it a difficult population [in which] to show superior benefit of guadecitabine.”

Dr. Azab added, “ASTRAL-1 is the largest global prospective study ever conducted in this specific patient population with low-intensity therapy, with 815 patients randomized, of whom about 90% were treated with hypomethylating agents (guadecitabine, azacitidine, or decitabine). The large body of clinical and genetic data will still provide the medical community with very valuable insights into the role of several prognostic clinical and genetic markers that may influence outcome with [hypomethylating agent] treatment….”

About the ASTRAL-1 Study

The ASTRAL-1 study evaluated the efficacy and safety of guadecitabine in adults with previously untreated AML who were not eligible for intensive induction chemotherapy. The study is the largest global prospective study ever conducted in this specific patient population, with 815 patients randomized from 163 investigator sites in 24 countries worldwide.

The study compared guadecitabine, delivered subcutaneously (SC) at 60 mg/m2/d for 5 days, with physicians’ choice of intravenous (IV) or SC azacitidine at 75 mg/m2/d for 7 days, decitabine at 20 mg/m2/d IV for 5 days, or low-dose cytarabine at 20 mg SC twice a day for 10 days, all administered in 28-day cycles.

In addition to the co-primary endpoints of overall survival and complete response rate, the study evaluated multiple secondary endpoints including progression-free survival, composite complete response, overnight stays in hospital, red cell/platelet transfusions, quality of life (EQ-5D-5L), duration of response, and safety.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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