CHICAGO–CPX-351, a liposomal formulation of cytarabine and daunorubicin, improved overall survival compared with a standard 7+3 regimen of cytarabine and daunorubicin in older patients with secondary acute myeloid leukemia (AML), according to final study results presented by Jeffrey E. Lancet, MD, from H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, at the 2016 ASCO Annual Meeting.
Based on results from this trial, the U.S. Food and Drug Administration granted breakthrough therapy designation to CPX-351 for the treatment of patients with therapy-related AML or AML with myelodysplasia-related changes on May 19, 2016.
The randomized, open-label, phase III trial compared first-line CPX-351 with 7+3 in 309 patients (age range = 60-75 years) with secondary AML enrolled at 39 sites across the United States and Canada. Patients were included in the trial if they had:
- untreated AML
- confirmation of therapy-related AML, AML with a history of myelodysplasia or chronic myelomonocytic leukemia, or AML with WHO-defined MDS-related cytogenetic abnormalities
- Eastern Cooperative Oncology Group performance status 0-2
Patients were randomized 1:1 to receive induction therapy with either CPX-351 (100 units/m2 administered intravenously on days 1, 3, and 5; n=153) or 7+3 (cytarabine 100 mg/m2 for 7 days and daunorubicin 60 mg/m2 on days 1-3; n=156). Study endpoints included overall survival (OS) and event-free survival (EFS), as well as complete remission/complete remission with incomplete blood count recovery (CR+CRi) and 60-day mortality.
Patients were well balanced for sex, race, age, performance status, AML-subtype, MDS-related cytogenetics, and prior hypomethylating therapy, the authors noted.
After a minimum follow-up of 13.7 months, Dr. Lancet and authors began their analysis of final results.
Compared with 7+3, CPX-351 resulted in superior OS (hazard ratio [HR] = 0.69; p=0.005), with median OS of 9.56 versus 5.95 months. CPX-351 also was more effective than standard therapy with respect to other study endpoints:
- EFS: HR=0.74 (p=0.021)
- CR+CRi response: 47.7% vs. 33.3% (p=0.016)
- 60-day mortality: 13.7% vs. 21.2% (p value not provided)
Adverse events (AEs) were similar in frequency and severity between the CPX-351 and 7+3 groups, with 92 percent and 91 percent of patients, respectively, experiencing grade 3-5 AEs in each group.
"Older patients with secondary AML have poor outcomes following front-line treatment with cytarabine and anthracycline," Dr. Lancet and authors wrote. Given the significant improvements in OS and EFS, without an increase in early mortality or AE frequency and severity, they concluded that "CPX-351 should become the standard of care for older patients with secondary AML."
Lancet JE, Uy GL, Cortes JE, et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. Abstract #7000. Presented at the 2016 ASCO Annual Meeting, June 4, 2016; Chicago, IL.