medwireNews: Phase III trial findings support the use of a liposome-encapsulated formulation of cytarabine and daunorubicin in older patients with a new diagnosis of high-risk secondary acute myeloid leukemia (AML).
The liposomal formulation – called CPX-351 – was associated with a significant 31% reduced risk for death relative to conventionally administered cytarabine and daunorubicin, with corresponding median overall survival times of 9.56 and 5.95 months, report Jeffrey Lancet (H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA) and colleagues.
The proportion of patients achieving complete remission or complete remission with incomplete neutrophil or platelet recovery was also significantly higher with the liposomal than standard formulation, at 47.4% versus 33.3%, as was the rate of complete remission alone, at 37.3% and 25.6%, respectively.
And median event-free survival was likewise significantly prolonged with CPX-351, at 2.53 months versus 1.31 months with standard cytarabine–daunorubicin.
Writing in the Journal of Clinical Oncology, the researchers explain that liposomal encapsulation enables a fixed ratio of the drugs to be maintained, “enabling intracellular delivery of the synergistic drug ratio and enhancing uptake in leukemia cells to a greater extent than normal cells,” which in their study translated into better outcomes.
The team also points out that “[t]he types of adverse events, proportions of patients who experienced them, and severities of events were comparable between treatment cohorts,” which given that the treatment phase was longer in the CPX-351 than control arm (median 62 vs 41 days) suggests the liposomal agent “may have a more favorable overall toxicity profile.”
Lancet et al conclude that “[c]ollectively, these clinical data support the adoption of CPX-351 for the initial treatment” of this patient population.
The trial included 309 patients aged 60–75 years with a diagnosis of therapy-related AML, AML with antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia, or de novo AML with MDS-related cytogenetic aberrations.
Participants who were randomly assigned to participate in the CPX-351 group received an initial induction course in which the agent was administered at a dose of 100 U/m2 (100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) on days 1, 3, and 5, while those in the control cohort received daily cytarabine 100 mg/m2 for 7 days plus daunorubicin 60 mg/m2 on days 1–3. Patients in both groups could receive a second induction course and up to two cycles of post-remission consolidation therapy with their assigned regimen.
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