The phase 3 ASCERTAIN study found that orally administered decitabine and cedazuridine had similar pharmacologic effects compared with intravenously administered decitabine.
Findings from the phase 3 ASCERTAIN study (NCT03306264) identified that fixed-dose oral decitabine and cedazuridine (Inqovi) had pharmacologic equivalence to intravenously (IV) administered decitabine in patients with intermediate and high-risk myelodysplastic syndromes (MDS), including chronic myelomonocytic leukemia (CMML).1
According to results published in The Lancet Hematology, the primary end point of total exposure of oral decitabine/cedazuridine compared with IV decitabine was 98.93% (90% CI, 92.66%-105.60%), indicating equivalent pharmacokinetic exposure.2 These findings identify an alternative and more convenient option for treatment administration.
Regarding safety, the safety profiles of oral decitabine/cedazuridine and IV decitabine were similar. The most common grade 3 or higher adverse events (AEs) were thrombocytopenia (61%), neutropenia (57%), and anemia (50%).2 These AEs were consistent with what is expected from treatment with parenteral hypomethylating agents.1 Five treatment-related deaths were reported, including 2 related to oral therapy and 3 related to IV treatment. All deaths were due to sepsis or pneumonia.2
"Until recently, azacitidine and decitabine, both widely used hypomethylating agents, were available only in parenteral form, requiring patients with MDS and CMML to travel to treatment centers daily for 5 or 7 consecutive days of each 28-day treatment cycle," said Guillermo Garcia-Manero, MD, professor, Department of Leukemia, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, Houston, and the lead author on the publication, in a press release.1 "The ASCERTAIN study has demonstrated that the orally delivered fixed dose combination of decitabine and cedazuridine is an alternative option to parenteral administration of decitabine for patients with these diseases. The observed median overall survival of greater than 30 months in the ASCERTAIN study compared with historical controls is encouraging."
The median overall survival (OS) among those in the trial was approximately 32 months and in the intent-to-treat population, the overall response rate was 62%. The percentage of patients in this trial who moved to transplantation reached 20%, which exceeded the expected transplantation rates in patients receiving hypomethylating agents for MDS and CMML.1
ASCERTAIN is a phase 3, randomized, multicenter, open-label, crossover study of oral decitabine and cedazuridine vs IV decitabine. A total of 133 patients received treatment.2 Patients were randomized to receive an oral combination of 100 mg cedazuridine and 35 mg decitabine 5 times per day in 28-day cycles or IV decitabine 20 mg/m2 for 1 hour 5 times per day for a 28-day cycle.3
The primary end point was total 5-day area under the curve exposures of decitabine. The secondary end points included incidence of AEs, pharmacokinetics, complete responses, partial responses, leukemia-free survival, and OS.
Patients were eligible for enrollment if they have an ECOG performance status of 0-1, adequate organ function, a life expectancy of at least 3 months, and had not received major surgery within 30 days of the first study treatment. Patients were not eligible for participation if they had received prior treatment with more than 1 cycle of azacitidine or decitabine, treatment with any investigational therapy within 2 weeks of receiving the study treatment, or treatment with any concurrent MDS therapies.3