NDLI: Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial

Content Provider	Springer Nature : BioMed Central
Author	Ravandi, Farhad Roboz, Gail J. Wei, Andrew H. Döhner, Hartmut Pocock, Christopher Selleslag, Dominik Montesinos, Pau Sayar, Hamid Musso, Maurizio Figuera-Alvarez, Angela Safah, Hana Tse, William Sohn, Sang Kyun Hiwase, Devendra Chevassut, Timothy Pierdomenico, Francesca La Torre, Ignazia Skikne, Barry Bailey, Rochelle Zhong, Jianhua Beach, C. L. Dombret, Herve
Abstract	Background Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors’ clinical experience treating patients in the trial. Methods QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. Results A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1–80) oral azacitidine treatment cycles or 6 (1–73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3–4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications. Conclusion Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy. Trial registration This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012.
Related Links	https://jhoonline.biomedcentral.com/counter/pdf/10.1186/s13045-021-01142-x.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	17568722
DOI	10.1186/s13045-021-01142-x
Journal	Journal of Hematology & Oncology
Issue Number	1
Volume Number	14
Language	English
Publisher	BioMed Central
Publisher Date	2021-08-28
Access Restriction	Open
Subject Keyword	Oncology Hematology Cancer Research Oral azacitidine CC-486 Safety Maintenance
Content Type	Text
Resource Type	Article
Subject	Hematology Cancer Research Oncology Molecular Biology
Journal Impact Factor	29.9/2023
5-Year Journal Impact Factor	27.1/2023

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