Oral Azacitidine Prolongs Survival in Patients with Acute Myeloid Leukemia

Web Exclusives — April 13, 2021

Induction chemotherapy leads to remission in many patients with acute myeloid leukemia (AML) aged ≥60 years; however, the disease relapses in the majority of the patients, and the overall survival (OS) is poor. For patients who are not candidates for hematopoietic stem-cell transplant, effective maintenance treatments for AML are needed that can reduce the risk for relapse and improve OS, without causing unacceptable adverse events or compromising quality of life.

In September 2020, the FDA approved azacitidine (Onureg) tablets for adults with AML who are not candidates for transplant. This approval was based on data from a recent study (Wei AH, et al. N Engl J Med. 2020;383:2526-2537).

This international, randomized, double-blind, placebo-controlled, phase 3 QUAZAR AML-001 study evaluated the efficacy and safety of oral azacitidine as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Eligibility criteria included patients aged ≥55 years, were in complete remission (regardless of complete blood count recovery), and were not candidates for transplant.

A total of 472 adults were randomized in a 1:1 ratio to azacitidine 300 mg (N = 238) or to placebo (N = 234) once daily, on days 1 to 14 of each 28-day treatment cycle. Patients had intermediate-risk (86%) or poor-risk (14%) cytogenetics and an Eastern Cooperative Oncology Group performance status score of ≤3.

The primary end point was OS. The secondary end points included relapse-free survival (RFS) and health-related quality of life.

With a median follow-up of 42.1 months, azacitidine led to a significant improvement in OS compared with placebo (24.7 months vs 14.8 months, respectively; P <.001). In a subgroup analysis, OS benefit was seen in the azacitidine group regardless of the baseline cytogenetic risk, initial response to induction chemotherapy, receipt of consolidation therapy, or measurable residual disease status at trial entry. The median RFS was also significantly longer in the azacitidine arm than in the placebo arm (10.2 months vs 4.8 months, respectively; P <.001).

In addition, azacitidine demonstrated a manageable safety profile consistent with that of injectable azacitidine. The grade 1 or 2 gastrointestinal adverse events that were common in both groups included nausea, vomiting, and diarrhea, which were controllable with antiemetic and antidiarrheal agents. The most common grade 3 or 4 hematologic adverse events were neutropenia (41% with azacitidine vs 24% with placebo), thrombocytopenia (22% vs 21%, respectively), and anemia (14% vs 13%, respectively). Overall, the quality of life was maintained throughout the treatment with azacitidine.

In this trial, azacitidine “maintenance therapy prolonged overall and relapse-free survival among patients with AML who were in remission after intensive chemotherapy,” concluded the researchers, noting that the benefits of azacitidine for patients with AML in other clinical contexts require further investigation.

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