This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m2 for 5-days with orally administered decitabine with cedazuridine (DEC-C), as well as the clinical efficacy and safety of DEC-C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC-IV or oral DEC-C (days 1-5 in a 28-day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC-C for subsequent treatment cycles until treatment discontinuation. Equivalent systemic decitabine exposures were demonstrated (5-day area under the curve ratio between the two decitabine formulations of 99.64 [90% confidence interval 91.23%, 108.80%]). Demethylation rates also were similar (≤1.1% difference). Median overall survival (OS), clinical response and safety profile with oral DEC-C were consistent with those previously observed with DEC-IV. Next-generation sequencing was performed to identify molecular abnormalities that impact OS and TP53 mutations were associated with a poor outcome. These findings support the use of oral DEC-C in patients with AML.

Azienda Ospedaliero Universitaria Maggiore Della Carità Novara Novara Italy

Department of Haematology 3rd Faculty of Medicine Charles University and Faculty Hospital University Hospital Královské Vinohrady Prague Czech Republic

Department of Haematology Oncology and Stem Cell Transplantation University of Freiburg Medical Center University of Freiburg Faculty of Medicine Freiburg Germany

Department of Haematooncology University Hospital Ostrava Ostrava Czech Republic

Division of Hematology Department of Internal Medicine Faculty of Medicine University of Debrecen Hungary

Fakultní Nemocnice Brno and Masaryk University Brno Czech Republic

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico SC Ematologia Milan Italy

Hospital General Universitario Gregorio Marañón Madrid Spain

Hospital Universitario Central de Asturias Instituo de Investigación Sanitaria del Principado de Asturias Instituto Universitario de Oncología del Principado de Asturias Oviedo Spain

Institut Català d'Oncologia Hospital Duran i Reynals Barcelona Spain

MDS Unit Hematology AOUC DMSC Università degli Studi di Firenze Firenze Italy

Philipps University Marburg and University Hospital Gießen and Marburg Marburg Germany

Queen Elizabeth 2 Health Sciences Centre Halifax Nova Scotia Canada

Sigmund Freud PrivatUniversität Wien Austria

Städtisches Klinikum Braunschweig Klinik für Hämatologie und Onkologie Braunschweig Germany

Taiho Oncology Inc Pleasanton California USA

Universitätsklinikum Leipzig Leipzig Germany

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