CPX-351, a liposomal formulation of cytarabine and daunorubicin, improved event-free survival, overall survival, and response compared with a traditional dose of cytarabine/daunorubicin in older patients with high-risk secondary acute myeloid leukemia.
CHICAGO-CPX-351, a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio, significantly improved event-free survival, overall survival, and response compared with a traditional dose of cytarabine/daunorubicin in older patients with high-risk secondary acute myeloid leukemia (AML), according to the results of a study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 (abstract 7000).
“CPX-351 demonstrated superior efficacy compared to 7+3”-cytarabine 100 mg/m2/day for 7 days with daunorubicin 60 mg/m2 on days 1, 2, and 3-“in all key efficacy parameters,” said study presenter Jeffrey E. Lancet, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. “We feel that CPX-351 should be considered standard first-line treatment of older patient with high-risk AML.”
AML is a disease of older people and survival is significantly worse in older patients. A previous phase II trial in this patient population showed an almost doubling of overall survival from 6.1 months with the 7+3 regimen compared with 12.1 months with CPX-351.
In this open-label, phase III trial, 309 patients with secondary AML were randomly assigned to induction therapy with CPX-351 or the 7+3 regimen of cytarabine/daunorubicin. All patients were aged 60 to 75 and had a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome or chronic myelomonocytic leukemia, or AML with WHO-defined myelodysplastic syndrome–related cytogenetic abnormalities.
After a minimum follow-up of 13.7 months, results showed that treatment with CPX-351 resulted in a 31% reduction in the risk for death compared with the 7+3 regimen (hazard ratio [HR], 0.69; P = .005). The median overall survival was 9.56 months with CPX-351 compared with 5.95 months with the 7+3 regimen of cytarabine/daunorubicin. Patients treated with CPX-351 also had a 26% improved event-free survival compared with the 7+3 regimen (HR, 0.74; P = .021). In addition, patients assigned CPX-351 also a had significantly improved rate of response (47.7% vs 33.3%; P = .016).
Looking at patients who ultimately underwent transplant, Lancet and colleagues conducted a landmark survival analysis at the time of transplant. Median survival was not yet reached in patients assigned CPX-351 compared with 10.25 months in patients assigned 7+3 (HR, 0.46; P = .0046).
“Even though the numbers are small, there appears to be a major difference in outcome favoring CPX compared with 7+3 in patients who actually went through transplant, and please keep in mind that the majority of patients that went to transplant did so during complete remission,” Lancet said.
Richard A. Larsen, MD, of the University of Chicago, was the discussant of this abstract. He said that “these data will be sufficient for FDA approval and after approval, this agent should be considered for frontline use in this subset of AML patients.”