Compared with placebo, treatment with CC-486, the oral formulation of the hypomethylating agent (HMA) azacitidine significantly improved red blood cell (RBC) transfusion independence in patients with lower-risk myelodysplastic syndromes (MDS) and RBC transfusion-dependent anemia and thrombocytopenia. However, while the overall death rates were similar between the placebo and CC-486 arms, more early deaths occurred in the CC-486 arm. Results from this placebo-controlled trial were published in the Journal of Clinical Oncology by Guillermo Garcia-Manero, MD, and colleagues.
A total of 216 patients were randomly assigned 1:1 to receive either CC-486 300 mg (n = 107) or placebo (n = 109) for 21 days of a 28-day cycle. The primary endpoint was RBC transfusion independence.
The median age of the cohort was 74 years (range = 30-89), and the median hemoglobin was 8.1 g/dL (range = 5.4-10.9). Participants had median platelet counts of 25×109/L (range = 5-73) and the median transfusion requirement was 6.7 units over 56 days.
Overall, 31% of patients who received CC-486 and 11% of placebo-treated patient achieved RBC transfusion independence lasting for 56 days or longer (p = 0.0002). Transfusion independence lasted for a median of 11.1 and 5.0 months, respectively.
More CC-486 patients than placebo patients had hemoglobin increases ≥1.5 g/dL from baseline (23.4% vs. 4.6%). Patients who received CC-486 also achieved a greater platelet hematologic improvement rate (24.3% vs. 6.5%).
Regarding toxicity, 90% of CC-486 patients and 73% of placebo patients experienced a grade 3-4 adverse event (AE). Low-grade gastrointestinal events were the most common AEs in both arms.
The overall mortality rate was similar for both arms, and median survival was similar (17.3 vs. 16.7 months, respectively; p = 0.88). The authors noted, however, that there more early death (between days 1 and 56) occurred in the CC-486 arm (n=16) than in the placebo arm (n=6). Most deaths were associated with infection.