Celator Pharmaceuticals has announced that Vyxeos (CPX-351), a liposomal formulation of cytarabine and daunorubicin, significantly improved overall survival compared with the cytarabine and daunorubicin 7+3 regimen in patients with high-risk acute myeloid leukemia (AML).1
Results showed that median overall survival was 9.56 months with Vyxeos vs 5.95 months with 7+3 (HR, 0.69; P=.005). This represents a 31% reduction in the risk of death with Vyxeos. The 2-year survival rate from randomization was 31.1% in the Vyxeos arm and 12.3% in the 7+3 arm.
“The overall survival advantage seen with CPX-351 compared to 7+3, along with a superior response rate and no increase in serious toxicity indicates that we’ll likely have a new standard of care for treating older patients with secondary AML,” said principal investigator Jeffrey E. Lancet, MD, senior member and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center. “This represents a major step forward for a very difficult-to-treat patient population.”
Vyxeos was also associated with a 47.7% induction response rate compared with 33.3% with 7+3 (P=.016). Sixty-day all-cause mortality was 13.7% and 21.2%, respectively.
In terms of safety, there were no substantial differences in the rate of grade 3 or higher hematologic and non-hematologic adverse events.
Based on these results, Celator Pharmaceuticals expects to submit a New Drug Application (NDA) for Vyxeos by the end of 2016.
For the phase 3 trial, researchers enrolled 309 patients aged 60 to 75 years at 39 sites in the United States and Canada. Participants were randomly assigned 1:1 to receive induction with Vyxeos 100 u/m2 on days 1, 3, and 5 via 90-minutes infusion or cytarabine 100 mg/m2/day by continuous infusion for 7 days and daunorubicin 60 mg/m2 on days 1, 2, and 3.
Patients then received second induction with Vyxeos 100 u/m2 on days 1 and 3 in Vyxeos arm, and cytarabine 100 mg/m2/day by continuous infusion and daunorubicin 60 mg/m2 on days 1 and 2 in the 7+3 arm.
Patients who achieved a complete remission or a complete remission with incomplete blood count recovery could receive consolidation therapy with Vyxeos 65 u/m2 on days 1 and 3, or cytarabine 100 mg/m2/day by continuous infusion for 5 days and daunorubicin 60 mg/m2 on days 1 and 2.
Vyxeos is a nano-scale co-formulation of cytarabine and daunorubicin at a synergistic 5:1 molar ratio. The formulation represents a novel strategy to developing combinations of drugs in which molar ratios of 2 agents with synergistic anti-tumor activity are encapsulated in a nano-scale liposome in order to maintain the desired ratio following administration to the patient.
- Celator announces phase 3 trial for VYXEOS™ (CPX-351) in patients with high-risk acute myeloid leukemia demonstrates statistically significant improvement in overall survival [news release]. Ewing, NJ: Celator Pharmaceuticals; March 14, 2016. http://ir.celatorpharma.com/releasedetail.cfm?ReleaseID=960543. Accessed March 16, 2016.