OBJECTIVES: CPX-351, a liposomal co-encapsulation of cytarabine+daunorubicin at a synergistic 5:1 ratio, is approved in the US for the treatment of adults with newly diagnosed, tAML/AML-MRC. A phase 3 study evaluated CPX-351 versus conventional cytarabine/daunorubicin (7+3) in adults aged 60-75 years with newly diagnosed, tAML/AML-MRC; the current analysis demonstrates the number needed to treat (NNT) as a measure of effect of CPX-351 versus 7+3.

METHODS: In the phase 3 study (NCT01696084), patients were randomized 1:1 to receive 1-2 induction cycles with CPX-351 (100 units/m [100 mg/m cytarabine and 44 mg/m daunorubicin] on Days 1, 3, 5 [2nd induction: Days 1, 3]) or 7+3 (cytarabine 100 mg/m/day continuously for 7 days [2nd induction: 5 days] + daunorubicin 60 mg/m on Days 1-3 [2nd induction: Days 1-2]). Responders could receive ≤2 consolidation cycles. The NNT to prevent 1 death at 2 years with CPX-351 versus 7+3 was calculated as the reciprocal of the absolute risk reduction (1/ARR), where ARR equaled the control death rate minus experimental death rate.

RESULTS: 153 and 156 patients were randomized to receive CPX-351 and 7+3, respectively. Patient characteristics were balanced between cohorts. Median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (hazard ratio, 0.69 [95% CI, 0.52-0.90]; 1-sided P = 0.003). By 2 years, 84% of patients in the 7+3 arm had died versus 67% in the CPX-351 arm. Thus, on average, for every 6 patients treated with CPX-351, 1 death would be prevented over 2 years compared with 7+3 (1/(0.84 – 0.67)). The CPX-351 safety profile was consistent with the known profile of 7+3.

CONCLUSIONS: CPX-351 improved survival versus 7+3, with an associated NNT of 6 to prevent 1 death at 2 years, supporting the treatment benefit of CPX-351 in adults with newly diagnosed, tAML/AML-MRC.