Multicenter phase 3 trial of oral decitabine-cedazuridine versus intravenous decitabine for MDS and CMML

The DNA methyltranferase inhibitors azacitidine and decitabine for patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) are available in parenteral form. Oral therapy with similar exposure for these diseases would offer potential treatment benefits. The multicenter crossover phase 3 ASCERTAIN trial, at 37 centers in Canada and the United States, randomized patients with MDS or CMML to oral decitabine-cedazuridine versus intravenous decitabine in the first cycle, followed by the other sequence in the second cycle. Primary endpoint of total exposure of oral versus intravenous therapy was 98.33%, indicating equivalent pharmacokinetic exposure on the basis of area under the curve. The safety profiles of both treatments were similar. There were five treatment-related deaths; two deemed related to oral therapy (sepsis and pneumonia) and three to intravenous treatment (two septic shock and one pneumonia). The authors conclude that these results support use of oral decitabine-cedazuridine as a safe and effective alternative to intravenous decitabine for patients with MDS or CMML.