The novel first-in-class agent CPX-351 liposome injection improved response rates and eventfree survival (EFS) in elderly patients with newly diagnosed acute myeloid leukemia (AML). Lead author Jeffrey E. Lancet, MD, H. Lee Moffitt Cancer Center, Tampa, Florida, who presented interim data from the phase II study, said responses were even more robust in high-risk patients.
CPX-351 targets and inhibits the CK2 kinase, an enzyme that contributes to the regulation of several proteins essential to cell proliferation and differentiation. CPX-351 encapsulates cytarabine and daunorubicin at a 5:1 ratio; it is designed to maximize the synergy between these 2 cytotoxic agents to induce apoptosis. Both drugs are commonly used in treating AML in a standard “7 3” regimen, said Lancet.
The phase II study compared CPX-351 with the conventional “7 3” regimen of cytarabine and daunorubicin in 126 patients aged 60 to 75 years with newly diagnosed AML. The primary endpoint of this ongoing study is the rate of complete remission (CR); secondary endpoints include 1-year overall survival (OS), duration of response, EFS, and 30- and 60-day mortality. Study arms were well balanced for demographics and disease characteristics. Patients aged >70 years, or those with secondary AML, or who had ≥3 chromosomal abnormalities were stratified as high risk, and all others were classified as standard risk.
At an approximately 2:1 ratio, patients were randomized to receive 10 units/m2 of CPX-351 on days 1, 3, and 5; or 100 mg/m2 of cytarabine daily for 7 days by continuous infusion combined with 60 mg/m2 of daunorubicin on days 1, 2, and 3. Follow-up was 1 year.
The experimental drug produced a better rate of remission (CR plus CR with incomplete neutrophil/ platelet recovery) than standard therapy (66.7% vs 51.2%, respectively). The CPX-351 arm also had a higher aplasia rate than the control arm (87.7% vs 71.1%, respectively). EFS reached a median of 5 months in the CPX-351 arm compared with 2 months in the control arm. No significant difference in OS was observed between the groups at 1 year, with a median OS of 14.7 months for the 85 patients receiving CPX-351 versus 12.9 months for the 41 patients assigned to standard therapy.
High-risk patients did much better on the experimental drug. For example, in patients with secondary AML, median EFS was 3.8 months and OS was 12.1 months for those taking CPX-351 CPX-351 Improves Response in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia compared with EFS of 1.4 months and OS of 6.1 months for those receiving standard therapy.
The CPX-351 arm had a higher rate of cytopeniaassociated adverse events, including febrile neutropenia, infections (all grades), bacteremia, petechiae, and ecchymoses. The groups had similarly low rates of cardiac events. Median time to platelet count recovery following induction was longer with CPX-351, which Lancet attributed to the drug’s preferential uptake in the bone marrow. No statistically significant difference in early deaths was observed between the treatment arms. All induction deaths (ie, deaths at 30 and 60 days) occurred among the high-risk subgroups. “Our findings suggest that CPX-351 may provide a long-sought opportunity to improve clinical outcomes over ‘7 3’ in previously untreated AML,” said Lancet. Based on these results, investigators are planning to conduct a phase II trial. Lancet JE, Cortes JE, Hogge DE, et al. Phase 2B randomized study of CPX-351 vs cytarabine daunorubicin in newly diagnosed AML patients aged 60-75. Presented at: 52nd ASH Annual Meeting and Exposition; December 4-7, 2010; Orlando, Florida.