Positive results have been reported from a phase 3 trial of cytarabine/daunorubicin liposome for injection (Vyxeos, Celator Pharmaceuticals) in patients with high-risk (secondary) acute myeloid leukemia (AML) compared with the standard-of-care regimen of cytarabine and daunorubicin known as 7+3. The trial met its primary endpoint, demonstrating a statistically significant improvement in overall survival.
The median overall survival for patients treated with cytarabine/daunorubicin was 9.56 months compared with 5.95 months for patients receiving 7+3, representing a 3.61-month improvement in favor of the liposome treatment. The hazard ratio was 0.69 (P = 0.005), which represented a 31% reduction in the risk of death compared with 7+3. The proportion of patients alive at 12 months after randomization was 42% in the cytarabine/daunorubicin arm compared with 28% in the 7+3 arm. The proportion of patients alive at 24 months after randomization was 31% in the cytarabine/daunorubicin arm compared with 12% in the 7+3 arm.
Cytarabine/daunorubicin also demonstrated a statistically significant improvement in the induction response rate (complete response [CR] plus CR with incomplete blood count recovery [CRi]) compared with 7+3 (48% vs. 33%, respectively; P = 0.016), and this significance was maintained for the analysis of CR alone (37% vs. 26%; P = 0.040). The 60-day all-cause mortality rate was 14% versus 21%, in favor of patients treated with cytarabine/daunorubicin.
No substantial difference in grade-3 or higher adverse events was observed between cytarabine/daunorubicin and 7+3. In the intent-to-treat population, grade-3 or higher hematological adverse events were similar for overall infections, febrile neutropenia, and bleeding events. In the intent-to-treat population, grade-3 or higher nonhematological adverse events were similar across all organ systems, including cardiac, gastrointestinal, general systems, metabolic disorders, musculoskeletal, nervous system, respiratory, skin, and renal.
Based on these results, Celator Pharmaceuticals expects to submit a new drug application for cytarabine/daunorubicin liposome injection to the FDA later this year.
Source: Celator Pharmaceuticals; March 14, 2016.