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FDA Approves Oral Decitabine–Cedazuridine Combo for Adults With MDS
On July 7, 2020, the FDA approved an oral combination of decitabine and cedazuridine (Inqovi; Astex Pharmaceuticals) for the treatment of adults with myelodysplastic syndromes (MDS), including pretreated and untreated, de novo and secondary MDS with certain subtypes (ie, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
The application for this approval was granted priority review by the FDA, and the approval was made based on data from 2 open-label, randomized, crossover clinical trials, ASTX727-01-B and ASTX727-02.
ASTX727-01-B included 80 adults with MDS (International Prognostic Scoring System [IPSS] Intermediate-1, Intermediate-2, or high-risk) or CMML and ASTX727-02 included 133 adults with MDS or CMML, including all French-American-British classification criteria and IPSS Intermediate-1, Intermediate-2, or high-risk prognostic scores.
Patients in both studies were randomized in a 1:1 ratio to receive the oral combination therapy (decitabine 35 mg and cedazuridine 100 mg) in cycle 1 and intravenous (IV) decitabine 20 mg/m2 in cycle 2 or the reverse sequence.
Both regimens were administered once daily on days 1 through 5 of a 28-day cycle, and as of cycle 3, all patients received the combo therapy once daily on days 1 through 5 of each 28-day cycle until disease progression or unacceptable toxicity occurred.
Findings from ASTX727-01-B showed a complete response (CR) rate of 18% (95% CI, 10-28) and the median duration of CR was 8.7 months. Approximately 50% of 41 patients dependent on red blood cell (RBC) and/or platelet transfusions at baseline became independent of RBC and platelet transfusions during any consecutive 56-day post-baseline period. Of 39 patients independent of RBC and platelet transfusions at baseline, 25 (64%) were consistently transfusion-independent during any consecutive 56-day post-baseline period.
Results from ASTX727-02 demonstrated a 99% geometric mean ratio of the 5-day cumulative decitabine AUC following 5 consecutive once daily doses of the combination therapy versus that of IV decitabine was (90% CI, 93-106)
With regard to efficacy, 21% of patients in ASTX727-02 achieved CR (95% CI, 15-29) with a median duration of CR 7.5 months. Among 57 patients dependent on RBC and/or platelet transfusions at baseline, 30 (53%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of 76 patients independent of RBC and platelet transfusions at baseline, 63% were consistently transfusion-independent during any 56-day post-baseline period.
The most frequently reported (≥20%) adverse reactions with the combination therapy include 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.—Hina M. Porcelli
Source: US Food and Drug Administration. FDA approves oral combination of decitabine and cedazuridine for myelodysplastic syndromes. July 7, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-oral-combination-decitabine-and-cedazuridine-myelodysplastic-syndromes. Accessed July 7, 2020.
