Single-Agent Clofarabine versus Standard Daunorubicin/Cytarabine Regimen As Induction and Consolidation Therapy in Older Adults with Newly Diagnosed AML: Results of the Phase 3 E2906 Trial
The standard induction therapy for older adults (age ?60 years) with newly diagnosed acute myeloid leukemia (AML) is daunorubicin plus cytarabine (DA). Clinical evidence indicates that a non–cytarabine-based regimen such as single-agent clofarabine induction and consolidation therapy is associated with lower toxicity and similar efficacy outcomes.1 Foran and colleagues reported on the results of the randomized North American Leukemia Intergroup phase 3 trial that evaluated the noninferiority of single-agent clofarabine versus standard DA regimen in patients aged ?60 years with newly diagnosed AML; the primary end point was overall survival (OS).2
A total of 727 patients were randomized; the median age was 68 years, and 30% of patients had unfavorable cytogenetics. The current analysis was done with 686 patients randomized 2 months prior to study end and excluding 90 with ongoing response evaluation. The complete response (CR) or CR with incomplete blood count recovery rates (CRp) were similar between the clofarabine and DA treatment arms (40.3% vs 44.4%), as was the 60-day mortality (13.1% vs 14.9%). The survival analysis showed that clofarabine treatment was associated with inferior OS compared with DA (hazard ratio, 1.41), with a median OS of 9.9 months and 13.8 months, respectively. These survival results also extended to several subgroups tested, including those aged over 70 years, with intermediate-risk cytogenetics, and those with no antecedent hematologic disorder. Based on these results, the Data Safety Monitoring Committee recommended suspension of new accrual to this trial and transitioned all active patients on clofarabine therapy to DA on February 23, 2015. However, grade 4/5 nonhematologic toxicities were significantly higher in patients treated with DA, both in the induction (27% vs 18%; P = .01) and consolidation (20% vs 6%; P = .0005) phases. Based on these results, the authors concluded that single-agent clofarabine was inferior to standard DA therapy for patients aged ?60 years with newly diagnosed AML who are fit for intensive therapy, and that DA remains the standard of care.
- Thomas DA, et al. J Clin Oncol. 2010;28:3880-3889.
- Foran JM, et al. ASH 2015. Abstract 217.