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Decitabine plus cedazuridine approved by the FDA for MDS

Nov 20, 2020

On July 7, 2020, the U.S. Food and Drug Administration (FDA) approved the oral combination of decitabine with cedazuridine (ASTX727) to treat adult patients with myelodysplastic syndromes (MDS).1

The novel combination has been approved for previously treated or untreated patients with de novo or secondary MDS and International Prognostic Scoring System (IPSS) low, intermediate-1, intermediate-2, or high-risk MDS. The label also includes the indication for MDS with the following French–American–British subtypes: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia.2

This approval is based on the results of two clinical trials that evaluated the safety and efficacy of the tablet containing a fixed combination of 35 mg decitabine plus 100 mg cedazuridine, taken once daily on Days 1–5 for a minimum of four 28-day cycles.

The phase I/II trial ASTX727-01-B (NCT02103478) reported a 60% response rate, including 21% of patients achieving a complete response (CR). After a median follow-up of 24.3 months, the median duration of CR was 13.3 months. Median overall survival for all patients enrolled was 18.3 months (95% CI, 9.1­–not estimable). This study also demonstrated that oral decitabine, combined with a cytidine deaminase inhibitor as cedazuridine, had an equivalent bioavailability to the intravenous decitabine.3

The phase III ASCERTAIN trial (NCT03306264) presented its preliminary results in 2019, but an updated analysis has been published for the 62nd American Society of Hematology (ASH) Annual Meeting & Exposition. The study enrolled 133 patients, and after a median follow-up of 12.6 months and a median number of cycles of eight (range, 1–18), the overall objective response was 61%, including the 21% of patients who achieved a CR. To date, the median time to CR is 4.3 months, and the median CR duration is 7.5 months (range, 1.6–17.5). Red blood cells or platelet transfusion independence has been achieved by 53% and 33% of transfusion-dependent patients at baseline, for eight and 16 consecutive weeks, respectively.4

The safety profile of the oral decitabine/cedazuridine is considered consistent with the adverse events previously described with intravenous decitabine, with no significant differences in incidence or Grade. In the ASCERTAIN study, the most frequent treatment-emergent adverse events of Grade ≥ 3 were as follows4:

  • neutropenia, 51.5%
  • thrombocytopenia, 50%
  • anemia, 40%
  • febrile neutropenia, 26%
  • leukopenia, 21%
  • pneumonia, 12%
  • sepsis, 7%

  1. S. Food and Drug Administration. FDA approves oral combination of decitabine and cedazuridine for myelodysplastic syndromes. Published Jul 7, 2020. Accessed Nov 17, 2020.
  2. S. Food and Drug Administration. INQOVI® (decitabine and cedazuridine) prescribing information. Revised Jul, 2020. Accessed Nov 17, 2020.
  3. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. 2020;136(6):674-683. DOI: 10.1182/blood.2019004143
  4. Savona MR, McCloskey JK, Griffiths EA, et al. Clinical efficacy and safety of oral decitabine/cedazuridine in 133 patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Blood. 2020;136 (Supplement 1):37-38. DOI: 1182/blood-2020-133855