Oral Inqovi Safe and Effective Alternative MDS, CMML Treatment

For adult patients with intermediate and high-risk myelodysplastic syndromes (MDS) such as chronic myelomonocytic leukemia (CMML), fixed-dose oral treatment with Inqovi (Dacogen [decitabine] and cedazuridine) is comparable in terms of safety and efficacy to intravenous Dacogen, according to recently published study findings.

“Oral (Inqovi) was pharmacologically and pharmacodynamically (the affect a drug has on the patient’s body) equivalent to intravenous (Dacogen),” researchers wrote in a study published in The Lancet Haematology. “The results support use of oral (Inqovi) as a safe and effective alternative to intravenous decitabine for treatment of individuals with myelodysplastic syndromes or chronic myelomonocytic leukemia.”

The study drew on the final results of the phase 3 ASCERTAIN clinical trial, which enrolled adults with MDS or CMML as well as patients with acute myeloid leukemia (AML) as separate cohorts, with the study published in The Lancet Haematology not including the results for the patients with AML.

Patients with an ECOG performance status of 0 or 1 (meaning they could perform daily tasks with little or no assistance) and a life expectancy of at least three months were randomly assigned to receive either receive one daily tablet of Inqovi for five days or intravenous Dacogen in a 28-day cycle followed by five days of the other formulation in the next treatment cycle, researchers reported. All patients then received oral treatment from the third cycle until the discontinuation of treatment and were then rolled over to a maintenance study following completion of the study.

One hundred thirty-three patients (87% of whom were men and 91% of whom were White) were treated between Feb. 8, 2018 and June 7, 2021, according to the study, which reported a median follow-up of 966 days, with researchers noting the study’s primary endpoint of total exposure of oral versus intravenous treatment was 98.93%, “indicating equivalent pharmacokinetic exposure,” with similar safety profiles between the two treatment methods.

Researchers reported that the most frequent grade 3 or higher side effects were thrombocytopenia (a low platelet count, 61%), neutropenia (a low count of white blood cells known as neutrophils, 57%) and anemia (a low red blood cell count, 50%), with a 31% incidence of serious side effects for the oral treatment and 18% for the intravenous treatment.

Researchers also noted that there had been five treatment-related deaths during the trial, with two— due to sepsis and pneumonia — found to be related to oral therapy and three — two due to septic shock and one due to pneumonia — related to the intravenous treatment.

The median overall survival (OS; the time a patient lives following treatment regardless of disease status) in the trial population was approximately 32 months, while the overall response rate (ORR; patients whose disease responded partially or completely to treatment) in the intent-to-treat population was 62% and 20% of the patients in the trial proceeded to transplantation, according to a news release from Taiho Oncology, Inc.

ASCERTAIN, described in the news release as “the first Phase 3 trial to demonstrate pharmacologic equivalence between an oral and an intravenous (IV) formulation of a hypomethylating agent for use in the treatment of patients with MDS or CMML,” resulted in Inqovi’s approval by the Food and Drug Administration (FDA) in 2020 for the treatment of adults with MDS and CMML.

"Until recently, (Vidaza) and (Dacogen), both widely used hypomethylating agents, were available only in parenteral form, requiring patients with MDS and CMML to travel to treatment centers daily for five or seven consecutive days of each 28-day treatment cycle," said Dr. Guillermo Garcia-Manero, professor, department of leukemia, division of cancer medicine, at The University of Texas MD Anderson Cancer Center in Houston and the lead author on the study. "The ASCERTAIN study has demonstrated that the orally delivered fixed dose combination of (Inqovi) is an alternative option to parenteral administration of (Dacogen) for patients with these diseases. The observed median overall survival of greater than 30 months in the ASCERTAIN study compared with historical controls is encouraging."

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