Chicago, IL—A novel compound called CPX-351 that combines 2 older drugs (cytarabine and daunorubicin) in a new drug-delivery platform improved survival among older patients with newly diagnosed, high-risk (secondary) acute myeloid leukemia (AML), according to results of a phase 3 trial presented at the American Society of Clinical Oncology 2016 Annual Meeting.
CPX-351 is a novel formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio within 100-nm diameter bilamellar liposomes. This ratio was proven to have maximized synergy and minimized antagonism in laboratory studies, and studies in an animal model of leukemia showed selective uptake of the liposomal formulation by leukemic cells, explained lead investigator Jeffrey E. Lancet, MD, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
Although the mechanisms of action are not clear, Dr Lancet suggested that the liposomal formulation may be beneficial for effecting drug penetration, or that the molar ratio may facilitate better complementary drug activity.
“We think, biologically, the ability to deliver the drugs in a synergistic ratio that is maintained provides an advantage over free drugs,” he told the audience.
The study enrolled 309 patients at 39 sites across North America. Patients were randomized to receive induction with 1 to 2 cycles of CPX-351 100 units/m2 on days 1, 3, and 5, or cytarabine 100 mg/m2 for 7 days and daunorubicin 60 mg/m2 for 3 days (the 7 plus 3 schedule), followed by 1 to 2 cycles of consolidation therapy in patients who achieved remission.
CPX-351 improved survival, with a median overall survival of 9.56 months compared with 5.95 months in the 7 plus 3 arm (P = .005). CPX-351 also improved event-free survival and response rate compared with the 7 plus 3 group.
The 60-day mortality rate was lower in patients treated with CPX-351 than in the 7 plus 3 arm: 13.7% versus 21.2%, respectively.
In the CPX-351 group, adverse events were the cause of death in 10.5% of patients and the cause of progressive AML in 3.3% of patients within 60 days. In the 7 plus 3 group, adverse events were the cause of death in 9.9% of patients and of progressive AML in 11.3% of patients.
Hematopoietic stem-cell transplantations were performed in 34% of patients in the CPX-351 group and in 25% of patients in the 7 plus 3 arm. Transplants led to more favorable outcomes in patients treated with CPX-351. At the time of transplantation, median overall survival had not been reached in the CPX-351 group and was 10.25 months in the 7 plus 3 arm (P = .0046).
CPX-351 clearly showed superior outcomes in this study, stated Richard A. Larson, MD, University of Chicago, IL.
“Three days of the CPX-351 provided significantly better survival than the 7 plus 3 regimen, with an improvement of median survival of 3.5 months….The bottom line is that more patients were alive at 24 months [in the experimental arm],” Dr Larson said. He suggested that the FDA would approve CPX-351 based on these data.