Decitabine With Cedazuridine (Inqovi®)

Decitabine with cedazuridine (Inqovi®) is now available on the Pharmaceutical Benefits Scheme (PBS). It is listed for the treatment of high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML). These conditions must be confirmed through a bone marrow biopsy report and full blood examination. In the case of myelodysplastic syndrome, the condition must also be classified as Intermediate-2 or high risk according to the International Prognostic Scoring System (IPSS).

Decitabine works as a nucleoside metabolic inhibitor and exerts its antineoplastic effects by phosphorylation and incorporation into DNA and inhibition of DNA methyl transferase, causing apoptosis. Cedazuridine inhibits cytidine deaminase (CDA), which is involved in the degradation of nucleosides, including decitabine. Concurrent administration of cedazuridine with decitabine enhances the oral bioavailability of decitabine via inhibition of first pass metabolism of decitabine in the gut and liver by CDA. Baseline complete blood cell count, serum hepatic panel and serum creatinine are required prior to initiation of Inqovi® 35/100. The recommended dose of Inqovi® 35/100 is one tablet containing 35 mg of decitabine and 100 mg of cedazuridine taken orally once daily on Day 1 through 5 of each 28-day cycle for a minimum of four cycles. Delay or reduction in the dose is recommended in case of haematologic toxicity.

Inqovi® was evaluated in Study ASTX727-01-B that included 80 adult patients with MDS (IPSS Intermediate-1, Intermediate-2, or high-risk) or CMML. Patients were randomised 1:1 to receive Inqovi® (35 mg decitabine and 100 mg cedazuridine) orally in Cycle 1 and decitabine 20 mg/m² intravenously in Cycle 2, or the reverse sequence. Of the 41 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 20 (49%) became transfusion independent during any consecutive 56-day post-baseline period. Among the 39 patients who were independent of both RBC and platelet transfusions at baseline, 25 (64%) remained transfusion-independent during any consecutive 56-day post-baseline period.

Adverse effects associated with Inqovi® (incidence ≥ 20%) are fatigue, constipation, haemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnoea, diarrhoea, rash, dizziness, febrile neutropenia, oedema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. Commonly reported Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and haemoglobin decreased.