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Overall survival (OS) of patients with acute myeloid leukemia (AML) receiving maintenance therapy with oral azacitidine (CC-4860) in the postremission setting was significantly improved compared with placebo. The findings from this study were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, FL.
The clinical benefit of maintenance therapy in patients with AML who are unable to tolerate hematopoietic stem cell transplantation (HSCT), particularly older patients, has not previously been established.
In this randomized, placebo-controlled, multicenter, phase 3 clinical trial (QUAZAR AML-001; ClinicalTrials.gov Identifier: NCT01757535), patients with de novo or secondary AML with intermediate- or poor-risk cytogenetics, an age of at least 55 years, and an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less who were not candidates for HSCT were randomly assigned in a 1:1 ratio to receive either CC-4860 or placebo for 14 days each month following achievement of a CR or a CR with incomplete count recovery (CRi) after receiving induction chemotherapy with or without consolidation chemotherapy. The primary study end point was OS, with secondary end points including relapse-free survival (RFS), safety and tolerability, and health-related quality of life (HRQoL).
Of the 472 patients randomly assigned to study drug or placebo, 238 received CC-4860 and 234 received placebo. Baseline patient characteristics included a median age of 68 years with a diagnosis of de novo AML in approximately 90% of patients. Most patients (86%) had disease characterized by intermediate-risk cytogenetics, with high-risk cytogenetics characterizing the disease in the remaining 14% of patients.
Following induction chemotherapy, 81% and 19% achieved a CR or a CRi, respectively, and the majority of patients (80%) also received consolidation therapy.
At a median follow-up of 41.2 months, the median number of cycles of CC-4860 and placebo delivered were 12 and 6, respectively. Median OS was 24.7 months in the CC-486 arm and 14.8 months for those receiving placebo (hazard ratio [HR], 0.69; 95% CI, 0.55-0.86; P =.0009). Significant prolongation of RFS was also noted for patients receiving CC-4860 vs placebo, with respective median RFS of 10.2 months and 4.8 months (HR, 0.65; 95% CI, 0.52-0.81; P =.0001).
Notably, these efficacy findings were observed irrespective of age, baseline cytogenetic risk category, CR/CRi status, or whether or not patients had received consolidation therapy.
Regarding the safety of CC-4860 maintenance therapy, adverse events occurring at the highest frequencies were nausea (65% [CC-486]; 24% [placebo]) and vomiting (60% [CC-486]; 10% [placebo]), although most of these were classified as grade 1 or 2 adverse events. Grade 3 or 4 neutropenia occurred more frequently in patients receiving CC-486 (41% vs 24%), although rates of grade 3 or 4 thrombocytopenia (23% vs 22%), and anemia (14% and 13%) were similar in the 2 study arms. There were no treatment-related deaths.
In addition, no changes in HRQoL compared with baseline occurred in patients receiving CC-4860 as maintenance therapy.
In his concluding remarks, Andrew H. Wei of The Alfred Hospital in Melbourne, Australia, stated that “CC-486 is the first maintenance therapy to provide statistically significant and clinically meaningful improvements in both OS and RFS in a broad range of patients in first remission following intensive chemotherapy, with or without consolidation.”
He further commented that “maintenance therapy with CC-486 represents a new potential therapeutic standard for patients aged 55 years and older with AML in first remission.”
Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
Wei AH, Döhner H, Pocock C, et al. The QUAZAR AML-001 maintenance trial: Results of a phase III international, randomized, double-blind, placebo-controlled study of CC-486 (oral formulation of azacitidine in patients with acute myeloid leukemia (AML) in first remission. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract LBA-3.
This article originally appeared on Cancer Therapy Advisor