The phase 3, randomized, double-blind, placebo-controlled QUAZAR AML-001 study evaluated CC-486, an oral formulation of the hypomethylating agent azacitidine (Onureg). It was determined that CC-486 results in significantly improved overall survival (OS) and relapse-free survival in patients with acute myeloid leukemia (AML) in their first complete remission (CR) following induction chemotherapy. However, it is important that AML maintenance therapy also not compromise health-related quality of life (HRQoL) for these patients, and as such, the QUAZAR study also included HRQoL outcomes.
Patients in the QUAZAR AML-001 study were aged ≥55 years, had intermediate- or poor-risk cytogenetics at initial presentation, and European Cooperative Oncology Group performance status ≤3. They also achieved CR or CR with incomplete hematologic recovery after induction chemotherapy with or without consolidation and were not allogeneic stem-cell transplant candidates. Half of the enrolled patients received CC-486 330 mg and half received placebo once daily for 14 days per 28-day treatment cycle. On day 1 of each cycle and at the end of treatment, HRQoL questionnaires, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale, and EQ-5D-3L were completed by the patients. Changes in scores on these questionnaires were considered clinically meaningful if they changed ≥3 points in either direction (improvement or worsening) on the FACIT-Fatigue scale or +0.08 (improvement) or –0.10 (worsening) on the EQ-5D-3L health utility index. To be considered part of the evaluable population, patients had an HRQoL assessment at baseline and at ≥1 postbaseline visits. This population included 225 patients in the CC-486 arm and 219 patients in the placebo arm.
Patient characteristics including age were similar between arms. The median number of treatment cycles were 12 and 7 for CC-486 and placebo, respectively. At baseline, >95% of patients were compliant with therapy, and at all postbaseline visits except end of treatment, the compliance rate was >85%. At baseline, patients had comparable levels of fatigue (low) and good HRQoL. In fact, the overall mean (± standard deviation) baseline FACIT-Fatigue score was 40.8 (±8.4) and mean EQ-5D-3L score was 0.80 (±0.12), which are comparable to scores for the general population.
For the duration of the study, there were no clinically meaningful differences in mean changes from baseline between the CC-486 arm and the placebo arm for FACIT-Fatigue. At cycles 22 and 23, there were significant differences in EQ-5D-3L scores between arms (lower for CC-886), but these differences were not clinically meaningful. In terms of proportion of patients with clinically meaningful decline in FACIT-Fatigue score, there were no differences between the 2 arms (with the exception of cycle 29) and there were also no differences for EQ-5D-3L at any visit. Researchers concluded that the differences noted by exception at cycles 22, 23, and 29 were likely due to chance. There were no differences between treatment arms in median time to deterioration of scores for either questionnaire.
Over the duration of the QUAZAR AML-001 study, the oral azacitidine formulation CC-486 did not result in a decline in HRQoL compared with placebo. Patients maintained low levels of fatigue and favorable HRQoL.
Reference
Roboz G, Döhner H, Pocock C, et al. Health-Related Quality of Life with CC-486 in Patients with Acute Myeloid Leukemia (AML) in First Remission Following Induction Chemotherapy (IC): Results from the Phase III QUAZAR AML-001 Trial. Presented at: 25th European Hematology Association Congress Virtual; June 11-21, 2020. Abstract S334.