CPX-351 Enables Administration of Consolidation Treatment in the Outpatient Setting and Increases the Time Spent out of the Hospital after Completion of AML Treatment Compared with 7+3

Introduction: CPX-351 is a liposomal formulation of a synergistic 5:1 molar ratio of cytarabine and daunorubicin for the treatment for Acute Myeloid Leukemia (AML). CPX-351 possesses important pharmacologic differences that favorably impact efficacy and safety and may confer certain benefits related to health care resource use (HRU). CPX-351 has been granted fast track approval by the FDA, based on Phase 2 clinical trial (Study 204) results (Lancet, et al., Blood. 2014;123(21):3239-3246). Study 204 was analyzed to develop directional data regarding the impact of CPX-351 on HRU in relation to its clinical benefit.

Materials and Methods: Baseline characteristics from Study 204 were checked to confirm balanced patient demographics and AML risk factors. Study treatment (CPX-351 vs. 7+3), and its administration (number of inductions and consolidations) and setting (inpatient vs. outpatient) were viewed in the context of patient outcomes (response, 60-day mortality, and transplant). Time spent within and outside the hospital, free of an event (starting from randomization until documentation of persistent disease, start of transplant, relapse, or death, whichever occurred first) were calculated and compared by treatment arm. An intent-to-treat (ITT) analysis was performed so that the experience for 10 patients who crossover to CPX-351 were attributed to 7+3. Statistical significance was assessed using a one-tailed t-test. All results are unadjusted for potential confounders and the study was not powered to showed statistical significant difference of HRU.

Results: 85 patients were randomized to CPX-351 and 41 to the 7+3 control arm. The two study arms were balanced for age, sex, race, AML type (de novo vs. secondary AML), performance status, and cytogenetic risk. The prospectively defined survival analysis of the secondary AML subgroup showed significant improvement in the CPX-351 arm (HR=0.51, p=0.04). 60-day mortality was also markedly improved following CPX-351 (4.7% vs. 14.6%).

CPX-351 patients were more likely to have only one induction (80% vs. 70.7%; p = 0.13) and more likely to respond to induction (66.7% vs. 51.2%; p = 0.07). Among responders, CPX-351 patients were more likely to achieve remission with one induction only (82.1% vs. 72.4%; p = 0.15).

A total of 52 patients who responded to induction went on to receive consolidation (CPX-351: n=37; 7+3: n=15). A much larger proportion of responding CPX-351 patients received consolidation in the outpatient setting (40.5% vs. 13.3%; p = 0.02), and had only one induction (86.5%; vs. 66.7%). Nearly all CPX-351 transplanted patients were responders compared with control (13CR/14 (92.9%) vs. 5CR/7 (71.4%); p =0.1).

The number of hospital admissions and total days spent in hospital are key contributors to HRU. CPX-351 patients had fewer hospital admissions per patient compared to 7+3 (mean 1.51 vs. 1.76, p < 0.05). CPX-351 induction in all patients was associated with more days in hospital (median 35 vs. 28 days) than 7+3. However, among responding patients total days in hospital for induction plus consolidation was similar (median 42 vs. 43 days) with fewer days of hospitalization required for consolidation in the CPX-351 arm (median 4 vs. 11 days). Although CPX-351 was associated with longer hospitalization for induction among all patients it was also associated with greater time spent outside of the hospital after completion of AML treatment (median: 129 vs. 76 days).

Discussion: CPX-351 is associated with better clinical outcomes, including, lower early death rates, higher response rates, and improved overall survival in specific patient subsets. This report provides the first evidence that number of hospitalizations per patient, a key driver of hospital costs, is significantly less for CPX-351 and that overall days in hospital is similar for CPX-351 and 7+3 among responding patients, with many CPX-351 patients receiving consolidation as outpatients. In addition, CPX-351 improves the duration and proportion of time spent as an outpatient following completion of AML treatment. A more robust analysis of HRU is planned for the Phase 3 trial.