Leukemias, lymphomas, and other hematologic cancers:
Indications for: INQOVI
Myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS with the French-American-British subtypes and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
Clinical Trials:
Study ASTX727-01-B (ClinicalTrials.gov Identifier: NCT02103478)
The open-label, randomized, 2-cycle, 2-sequence crossover study included 80 adults with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). Patients were randomly assigned to receive Inqovi orally in cycle 1 and decitabine 20mg/m2 intravenously in cycle 2 or the reverse sequence. Both Inqovi and IV decitabine were administered once daily on days 1 through 5 of the 28-day cycle. Starting with cycle 3, all patients received Inqovi orally once daily on days 1 through 5 of each 28-day cycle until disease progression or unacceptable toxicity.
The median follow-up time was 24 months (range, 12-28.8 months) and the median duration of treatment was 6.6 months (range, <0.1-27.9). Results showed that 18% (95% CI, 10-28) of patients had a complete response (CR) with a median duration of CR of 8.7 months (95% CI, 1.1-18.2). The median time to CR was 4.8 months (95% CI, 1.7-10).
Among patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline (n=41), 49% became transfusion independent during any consecutive 56-day post baseline period. Among patients who were independent of transfusions at baseline (n=39), 64% remained transfusion-independent during any consecutive 56-day post baseline period.
Study ASTX727-02 (ClinicalTrials.gov Identifier: (NCT03306264)
The open-label, randomized, 2-cycle, 2-sequence crossover study that included 133 adult patients with MDS or CMML. Patients were randomly assigned to receive Inqovi orally in cycle 1 and decitabine 20mg/m2 intravenously in cycle 2 or the reverse sequence. Both Inqovi and IV decitabine were administered once daily on days 1 through 5 of the 28-day cycle. Starting with cycle 3, all patients received Inqovi orally once daily on days 1 through 5 of each 28-day cycle until disease progression or unacceptable toxicity.
The median follow-up time was 12.6 months (range, 9.3-20.5) and median duration of treatment was 8.2 months (range, 0.2-19.7). Results showed that 21% (95% CI, 15-29) of patients had a CR with a median duration of CR of 7.5 months (95% CI, 1.6-17.5). The median time to CR was 4.3 months (95% CI, 2.1-15.2).
Among patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline (n=57), 53% became transfusion independent during any consecutive 56-day post baseline period. Among patients who were independent of transfusions at baseline (n=76), 63% remained transfusion-independent during any consecutive 56-day post baseline period.
Adult Dosage:
Not substitutable for an IV decitabine product within a cycle. May premedicate with antiemetics. Swallow whole. Take on empty stomach. 1 tab once daily on Days 1 through 5 of each 28-day cycle. Give for a minimum of 4 cycles until disease progression or unacceptable toxicity. Dose modifications for adverse reactions: see full labeling.
Children Dosage:
Not established.
INQOVI Warnings/Precautions:
Risk of myelosuppression, infectious complications. Obtain CBCs at baseline, prior to each cycle, and as needed to monitor response and toxicity (see full labeling). Delay the next cycle if ANC <1000/microliter and platelets <50000/microliter in absence of active disease. Renal impairment (moderate): monitor; severe or ESRD: not studied. Embryo-fetal toxicity. Advise to use effective contraception during and for 6 months (females of reproductive potential) or 3 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥2 weeks after the last dose).
INQOVI Classification:
Nucleoside analogue + cytidine deaminase inhibitor.
INQOVI Interactions:
Avoid concomitant drugs metabolized by cytidine deaminase.
Adverse Reactions:
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, lab abnormalities (decreased leukocytes, platelet count, neutrophil count, and hemoglobin); febrile neutropenia, pneumonia, sepsis.
Drug Elimination:
Decitabine: Half-life 1.5 hours
Cedazuridine: Half-life: 6.7 hours; 46% excreted in urine, 51% excreted in feces
Generic Drug Availability:
NO
How Supplied:
Tabs—5 (blister card)
