Oral Decitabine Cedazuridine Safe, Effective Alternative to Intravenous Decitabine for Patients With MDS or CML

The use of oral decitabine cedazuridine is a safe and effective alternative to intravenous decitabine for treatment of those with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CML), according to phase 3 study results.

Study investigators enrolled 133 patients aged 18 years or older among 37 academic and community-based clinics in Canada and the United States. These patients received intravenous decitabine, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and a life expectancy of at least 3 months. The primary end point was measured as total decitabine exposure over 5 days with oral decitabine cedazuridine versus intravenous decitabine for cycles 1 and 2.

Participants were randomly assigned on a 1-to-1 basis to receive 5 days of oral decitabine cedazuridine (1 tablet once daily containing 35 mg decitabine and 100 mg cedazuridine as a fixed-dose combination) or intravenous decitabine (20 mg/m² per day by 1 hour of intravenous infusion) in a 28-day treatment cycle, followed by 5 days of the other formulation in the next treatment cycle. Following this, all patients received oral decitabine cedazuridine from the third cycle on until treatment discontinuation. Additionally, the median follow-up was 966 days (IQR 917 to 1050).

Results demonstrated that the primary end point of total exposure of oral decitabine cedazuridine vs intravenous decitabine was 98.93% (90% confidence interval [CI], 92.66 to 105.60), indicating equivalent pharmacokinetic exposure on the basis of area under the curve. It was noted that the safety profiles of oral decitabine cedazuridine and intravenous decitabine were similar. 

The most frequent adverse events of grade 3 or worse were thrombocytopenia (81 [61%] of 133 participants), neutropenia (76 [57%] participants), and anemia (67 [50%] participants). The incidence of serious adverse events in cycles 1 to 2 was 31% (40 out of 130 participants) with oral decitabine cedazuridine and 18% (24 out of 132 participants) with intravenous decitabine. There were 5 treatment-related deaths; 2 were related to oral therapy (sepsis and pneumonia) and 3 to intravenous treatment (septic shock and pneumonia).

Guillermo Garcia-Manero, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and colleagues concluded, “The results support use of oral decitabine–cedazuridine as a safe and effective alternative to intravenous decitabine for treatment of individuals with myelodysplastic syndromes or chronic myelomonocytic leukemia.”

“Oral decitabine–cedazuridine was pharmacologically and pharmacodynamically equivalent to intravenous decitabine,” they added.

Source:

Garcia-Manero G, McCloskey J, Griffiths E, et al. Oral decitabine–cedazuridine versus intravenous decitabine for myelodysplastic syndromes and chronic myelomonocytic leukemia (ASCERTAIN): A registrational, randomized, crossover, pharmacokinetics, phase 3 study. Lancet Hematol. Published online January 2024. doi: 10.1016/S2352-3026(23)00338-1