Phase (ph) 3 study of eribulin (ERI) vs dacarbazine (DTIC) in leiomyosarcoma (LMS) and liposarcoma (LPS) patients (pts)

Abstract

Background: In a ph 2 study, 32% and 47% of LMS and LPS pts, respectively, treated with ERI achieved progression‐free survival (PFS) at 12 wks. This ph 3 study (NCT01327885, in press) compared overall survival (OS) in advanced LMS and LPS pts treated with ERI or DTIC. Methods: Pts ≥18 yrs with advanced LPS/LMS, ECOG ≤2, and ≥2 prior systemic therapies (including anthracycline), were randomized 1:1 to ERI (1.4 mg/m2, IVon D1+D8) or DTIC (850, 1000, or 1200 mg/m2, IV on D1) every 21‐D until disease progression. Endpoints included OS (primary) and PFS and safety (secondary). Results: Overall, 452 pts (34% LPS; 66% LMS) were randomized (228 ERI; 224 DTIC). Median OS for ERI and DTIC was 13.5 and 11.5 mo, respectively (HR=0.77, 95% CI 0.62‐0.95; P=0.02). PFS was 2.6 mo/arm (HR=0.88, 95% CI 0.71‐1.09; P=0.23). In Eastern Europe, Latin America, Asia (R3), median OS was 11.4 (ERI) and 9.7 mo (DTIC; HR=0.67, 95% CI 0.38‐1.17; P=0.16) and improved in both LPS (18.4 vs 10.1 mo) and LMS pts (9.4 vs 7.9 mo). Overall, median OS for ERI vs DTIC was 15.6 vs 8.4 mo in LPS (HR=0.51, 95% CI 0.35‐0.75; P<0.001) and 12.7 vs 13.0 mo in LMS (HR=0.93, 95% CI 0.71‐1.20; P=0.57). In LMS pts, median OS was 14.2 vs 9.7 mo in males (HR=0.64, 95% CI 0.37‐1.14) and 12.7 vs 14.8 mo in females (HR=1.13, 95% CI 0.85‐1.50). Median OS in the ERI arm improved in females with nonuterine vs uterine LMS (14.6 vs 9.4 mo; HR=0.64, 95% CI 0.43‐0.95). Adverse events (AEs) were more frequent with ERI vs DTIC, including neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20% vs 4%), and alopecia (35% vs 3%); as were grade (G) 3 (39% vs 36%), G4 (24% vs 19%), and G5 AEs (4% vs 1%). Thrombocytopenia was more frequent in DTIC vs ERI (28% vs 6%). AEs in R3 were similar. Conclusions: This ph 3 trial of ERI met its primary objective of OS benefit in pts with advanced LMS/LPS. Toxicity profile was consistent with prior experience, with no new safety findings. Eisai Inc.