In a pivotal phase III trial reported in the Journal of Clinical Oncology, Lancet et al found that cytarabine and daunorubicin liposome (CPX-351, Vyxeos) significantly improved overall survival vs standard cytarabine plus daunorubicin (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). The study supported the approval of CPX-351 for treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes in September 2017.
In the open-label trial, 309 patients aged 60 to 75 years with newly diagnosed high-risk/sAML enrolled between December 2012 and November 2014 at 39 sites in the United States and Canada were randomized to receive one to two induction cycles of CPX-351 (n = 153) or 7+3 (n = 156) followed by consolidation therapy with a similar regimen. The initial CPX-351 induction course consisted of 100 units/m2 (100 mg/m2 cytarabine and 44 mg/m2 daunorubicin) via 90-minute infusion on days 1, 3, and 5. The initial 7+3 induction course consisted of cytarabine 100 mg/m2/d via 7-day continuous infusion with daunorubicin 60 mg/m2 on days 1 to 3.
The primary endpoint was overall survival.
Median follow-up was 20.7 months. Median overall survival was 9.56 months in the CPX-351 group vs 5.95 months in the 7+3 group (hazard ratio [HR] = 0.69, P = .003). Estimated overall survival was 41.5% vs 27.6% at 1 year and 31.1% vs 12.3% at 2 years. Benefit of CPX-351 was observed across AML subtypes and age in prespecified subgroup analyses. Overall remission rates were 47.7% vs 33.3% (P = .016). Median event-free survival was 2.53 vs 1.31 months (HR = 0.74, P = .021).
The incidence of nonhematologic adverse events were similar in the two groups. The CPX-351 group had a longer treatment phase and prolonged time to neutrophil (median 35 vs 29 days) and platelet count (36.5 vs 29 days) recovery. The most common grade ≥ 3 adverse events in the CPX-351 group were febrile neutropenia (68.0% vs 70.9%), pneumonia (19.6% vs 14.6%), and hypoxia (13.1% vs 15.2%). Early mortality rates with CPX-351 vs 7+3 were 5.9% vs 10.6% (P = .149) through day 30 and 13.7% vs 21.2% (P = .097) through day 60.
The investigators concluded, “CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.”
The study was supported by Celator Pharmaceuticals, a subsidiary of Jazz Pharmaceuticals.
Jeffrey E. Lancet, MD, of the H. Lee Moffitt Cancer Center and Research Institute, is the corresponding author for the Journal of Clinical Oncology article.
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