Ascertaining QUAZARs: slow-motion and light-speed development of oral azacitidine and decitabine

Abstract

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are devastating diseases that frequently rely on the use of parenteral hypomethylating agents (HMAs), either as monotherapy or in combination, as first-line treatment for many patients. Two new oral HMAs, decitabine/cedazuridine (DC) for use in place of azacitidine or decitabine in MDS, and azacitidine (CC-486) for use as maintenance treatment in AML, were recently approved by the FDA. We will discuss the development of these oral HMAs, including the advantages/disadvantages in transitioning to oral HMAs and an in depth look at the pivotal phase III trials that led to their FDA approval – ASCERTAIN for DC and QUAZAR-AML-001 for CC-486. We also review how these agents have been and are being studied in other malignancies, and examine the future role that these exciting novel agents will play in both MDS and AML.

Keywords:

• Hypomethylating agent
• azacitidine
• decitabine
• myelodysplastic syndromes
• acute myeloid leukemia
• oral chemotherapy

Acknowledgements

The authors acknowledge Erin Demakos RN, Darshanie Sewah RN, Kayla Varga NP, Saudia Alli NP, Sheila Navida-Basila, Kevin Sprotte, and Tina Czaplinska.

Disclosure statement

JF and SN report no competing interests to declare; DT reports contracted research funding paid to his institution from Astellas Pharma and consulting fees from AbbVie and CTI Biopharma; LS reports contracted research funding paid to his institution from Celgene/BMS.