Oral decitabine/cedazuridine versus intravenous decitabine for acute myeloid leukaemia: A randomised, crossover, registration, pharmacokinetics study
Klaus Geißler, Zdeněk Kořı́stek, Teresa Bernal, Jan Novák, Gabriela Rodríguez‐Macías, Stephan Metzelder, Árpád Illés, Jiřı́ Mayer, Montserrat Arnán, Mary‐Margaret Keating, Jürgen Krauter, Monia Lunghi, Nicola Stefano Fracchiolla, Uwe Platzbecker, Valeria Santini, Yuri Sano, Aram Oganesian, Harold Keer, Michael Lübbert
Abstract
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.