itive: 16%, negative: 74%), triple negative status (ER-, PR-, HER2/neu-: 19%), presence of visceral disease (82%, including 60% liver and 38% lung) and bone disease (61%), and number of sites of metastases (greater than two: 50%), were also similar in the HALAVEN and control arms. Patients received a median of four prior chemotherapy regimens in both arms.
In Study 1, a statistically significant improvement in overall survival was observed in patients randomized to the HALAVEN arm compared to the control arm (see Table 5). An updated, unplanned survival analysis, conducted when 77% of events had been observed (see Figure 1), was consistent with the primary analysis. In patients randomized to HALAVEN, the objective response rate by the RECIST criteria was 11% (95% CI: 8.6%, 14.3%) and the median response duration was 4.2 months (95% CI: 3.8, 5.0 months).
Table 5: Comparison of Overall Survival in HALAVEN and Control Arm - Study 1 Overall Survival HALAVEN
(n=508) Control Arm
(n=254)
Primary survival analysis
Number of deaths 274 148
Median, months (95% CI) 13.1 (11.8, 14.3) 10.6 (9.3, 12.5)
Hazard Ratio (95% CI)a 0.81 (0.66, 0.99)
P valueb 0.041
Updated survival analysis
Number of deaths 386 203
Median, months (95% CI) 13.2 (12.1, 14.4) 10.6 (9.2, 12.0)
CI = confidence interval
a Based on Cox proportional hazards model stratified by geographic region, HER2 status, and prior capecitabine therapy.
b Based on a log-rank test stratified by geographic region, HER2 status, and prior capecitabine therapy.
Figure 1: Updated Overall Survival Analysis for Study 1
14.2 Liposarcoma The efficacy and safety of HALAVEN were eva luated in Study 2, an open-label, randomized (1:1), multicenter, active-controlled trial. Eligible patients were required to have unresectable, locally advanced or metastatic liposarcoma or leiomyosarcoma, at least two prior systemic chemotherapies (one of which must have included an anthracycline), and disease progression within 6 months of the most recent chemotherapy regimen. Patients were randomized to HALAVEN 1.4 mg/m2 administered intravenously on Days 1 and 8 of a 21-day cycle or to dacarbazine at a dose of 850 mg/m2, 1000 mg/m2, or 1200 mg/m2 administered intravenously every 21 days (dacarbazine dose was selected by the investigator prior to randomization). Treatment continued until disease progression or unacceptable toxicity. Randomization was stratified by histology (liposarcoma or leiomyosarcoma), number of prior therapies (2 vs. > 2), and geographic region (U.S. and Canada vs. Western Europe, Australia, and Israel vs. Eastern Europe, Latin America, and Asia). The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were progression-free survival (PFS) and confirmed objective response rate (ORR) as assessed by the investigator according to Response eva luation Criteria in Solid Tumors (RECIST v1.1). Patients in the dacarbazine arm were not offered HALAVEN at the time of disease progression.
A total of 446 patients were randomized, 225 to the HALAVEN arm and 221 to the dacarbazine arm. The median age was 56 years (range: 24 to 83); 33% were male; 73% were White; 44% had ECOG performance status (PS) 0 and 53% had ECOG PS 1; 68% had leiomyosarcoma and 32% had liposarcoma; 39% were enrolled in U.S. and Canada (Region 1) and 46% were enrolled in Western Europe, Australia, and Israel (Regio |
