FDA Approves Decitabine and Cedazuridine Combination for MDS

The FDA approved an oral combination of decitabine and cedazuridine for adults with myelodysplastic syndromes (MDS), including:

  • those with previously treated and untreated, de novo, and secondary MDS with the following French-American-British subtypes: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia (CMML)
  • those with intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System (IPSS) disease

Approval was based on results from two open-label, randomized trials. The first trial, ASTX727-01-B, included 80 adults with Intermediate-1, Intermediate-2, or high-risk MDS or CMML. The second, trial ASTX727-02, enrolled 133 patients with MDS or CMML, including all French-American-British classification criteria and IPSS groups. Each trial randomized participants 1:1 to receive either decitabine 35 mg and cedazuridine 100 mg orally, followed by decitabine 20 mg/m2 intravenously or the reverse sequence for two 28-day cycles until disease progression or unacceptable toxicity. Both groups received a third cycle of the combination treatment.

In ASTX727-01-B, 18% of patients achieved a complete response (CR) with a median response duration of 8.7 months. Of 41 patients who were red blood cell (RBC) or platelet transfusion-dependent, 49% no longer required transfusion during any consecutive 56-day post-baseline period (n=20). Approximately two-thirds of the remaining 39 patients who were not dependent on RBC or platelet transfusions at baseline maintained this status during the same 56-day period (n=25).

In ASTX727-02, 21% of patients achieved CR with a median response duration of 7.5 months. More than one half (53%) of the 57 RBC and platelet transfusion-dependent patients became independent during any 56-day post-baseline period (n=30), and 63% of the 76 transfusion-independent patients remained so (n=47).

The most common adverse events (occurring in >20% of patients) were fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased.

The combination treatment is approved at a dosage of decitabine 35 mg and cedazuridine 100 mg, taken orally once daily on days 1 through 5 of each 28‑day cycle.

Source: FDA press release, July 7, 2020.