n 2); and 47% received more than two prior systemic chemotherapies. The most common (>40%) prior systemic chemotherapies were doxorubicin (90%), ifosfamide (62%), gemcitabine (59%), trabectedin (50%), and docetaxel (48%).
Of the 143 patients with liposarcoma, the median age was 55 years (range: 32 to 83); 62% were male, 72% were White; 41% had ECOG PS of 0 and 53% had ECOG PS of 1; 35% were enrolled in Region 1 and 51% were enrolled in Region 2; and 44% received more than two prior systemic chemotherapies. The distribution of subtypes of liposarcoma, based on local histologic assessment, were 45% dedifferentiated, 37% myxoid/round cell, and 18% pleomorphic.
Study 2 demonstrated a statistically significant improvement in OS in patients randomized to HALAVEN compared with dacarbazine (see Table 6). There was no significant difference in progression-free survival in the overall population. Treatment effects of HALAVEN were limited to patients with liposarcoma based on pre-planned, exploratory subgroup analyses of OS and PFS (see Tables 6 and 7 and Figure 2). There was no evidence of efficacy of HALAVEN in patients with advanced or metastatic leiomyosarcoma in Study 2 (see Table 7).
Table 6: Efficacy Results for the Liposarcoma Stratum and All Patients* in Study 2a Liposarcoma
Stratum All Patients*
Halaven
(n=71) Dacarbazine
(n=72) Halaven
(n=225) Dacarbazine
(n=221)
Overall survival
Deaths, n (%) 52 (73) 63 (88) 173 (77) 179 (81)
Median, months
(95% CI) 15.6
(10.2, 18.6) 8.4
(5.2, 10.1) 13.5
(11.1, 16.5) 11.3
(9.5, 12.6)
Hazard ratio (HR)
(95% CI) 0.51
(0.35, 0.75) 0.75
(0.61, 0.94)
Stratified log-rank p value N/A† 0.011
Progression-free survival
Events, n (%) 57 (80) 59 (82) 194 (86) 185 (84)
Disease progression 53 52 180 170
Death 4 7 14 15
Median, months
(95% CI) 2.9
(2.6, 4.8) 1.7
(1.4, 2.6) 2.6
(2.0, 2.8) 2.6
(1.7, 2.7)
HR
(95% CI) 0.52
(0.35, 0.78) 0.86
(0.69, 1.06)
Objective response rate
Objective response rate (%)
(95% CI) 1.4
(0, 7.6) 0
(0, 4.2) 4.0
(1.8, 7.5) 5.0
(2.5, 8.7)
a Efficacy data from one study site enrolling six patients were excluded.
*All patients = liposarcoma and leiomyosarcoma.
† N/A = not applicable
Figure 2: Kaplan-Meier Curves of Overall Survival in the Liposarcoma Stratum in Study 2
Table 7: Efficacy Results for the Leiomyosarcoma Stratum in Study 2a Leiomyosarcoma
Stratum
Halaven
(n=154) Dacarbazine
(n=149)
Overall survival
Deaths, n (%) 121 (79) 116 (78)
Median, months
(95% CI) 12.8
(10.3, 14.8) 12.3
(11.0, 15.1)
HR (95% CI) 0.90 (0.69, 1.18)
Progression-free survival
Events, n (%) 137 (89) 126 (85)
Disease progression 127 118
Death 10 8
Median, months
(95% CI) 2.2
(1.5, 2.7) 2.6
(2.2, 2.9)
HR (95% CI) 1.05 (0.81, 1.35)
Objective response rate (%)
(95% CI) 5.2
(2.3, 10) 7.4
(3.7, 12.8)
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