Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI).

Session Type and Session Title: 
Oral Abstract Session, Sarcoma
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA10502)
Patrick Schöffski, Robert G. Maki, Antoine Italiano, Hans Gelderblom, Giovanni Grignani, Veridiana Pires De Camargo, Sebastian Bauer, Sun Young Rha, Sant P. Chawla, Jean-Yves Blay, Peter Hohenberger, David R. D'Adamo, Benjamin Wang, Bartosz Chmielowski, Axel Le Cesne, George D. Demetri, Shreyaskumar Patel; University Hospital Leuven, Leuven, Belgium; Mount Sinai Medical Center, New York, NY; CLCC Institut Bergonié, Bordeaux, France; Leiden University Medical Center, Leiden, Netherlands; Fondazione del Piemonte per l’Oncologia IRCC, Candiolo, Italy; Hospital Sírio-Libanês, São Paulo, Brazil; West German Cancer Center, Essen, Germany; Severance Hospital, Seoul, South Korea; Sarcoma Oncology Center, Santa Monica, CA; Université Claude Bernard & Centre Léon Bérard, Lyon, France; Mannheim University Medical Center, Mannheim, Germany; Eisai Inc, Woodcliff Lake, NJ; Eisai, Woodcliff Lake, NJ; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA; Institut Gustave Roussy, Villejuif, France; Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX

Abstract Disclosures


Background: In a phase II study of pts with advanced soft tissue sarcoma, 32% and 47% of pts with LMS and ADI respectively, treated with the microtubule dynamics inhibitor eribulin achieved progression-free survival (PFS) at the 12 wk timepoint (Schöffski et al. Lancet Oncol. 2011; NCT00413192). Based on these findings, this phase III study (NCT01327885) compared overall survival (OS) in pts with advanced LMS and ADI treated with eribulin or dacarbazine. Methods: Pts aged ≥ 18 yrs with advanced high/intermediate grade LMS or dedifferentiated, myxoid, round cell or pleomorphic variants of ADI incurable by surgery and/or radiotherapy were enrolled. Pts had ECOG status ≤ 2 and had received ≥ 2 standard systemic treatment regimens including an anthracycline. Pts were randomized 1:1 to eribulin (1.4 mg/m2, IV on D1 and D8) or dacarbazine (850–1200 mg/m2, IV on D1) every 21 days until disease progression. Primary endpoint was OS. Secondary endpoints included PFS, PFS rate at Wk 12 and safety. Results: Overall, 452 pts (67% female; 79% < 65 yrs) were randomized (228 eribulin; 224 dacarbazine). Median OS for eribulin and dacarbazine was 13.5 and 11.5 months, respectively (HR = 0.768, 95% CI 0.618–0.954; P= 0.017). PFS was 2.6 months in both arms (HR = 0.877, 95% CI 0.710–1.085; P= 0.229). PFS rate at Wk 12 was 33% and 29% for eribulin and dacarbazine, respectively. In eribulin and dacarbazine arms, respectively, 26% and 14% of pts required dose reductions and 8% and 5% discontinued due to treatment-emergent adverse events (TEAEs). TEAEs were more frequent in eribulin than dacarbazine arm, including neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20% vs 4%) and alopecia (35% vs. 3%); as were TEAEs of grade 3 (63% vs 53%), grade 4 (26% vs 20%), and fatal TEAEs (4% vs 1%). Thrombocytopenia was more frequent in dacarbazine than eribulin arm (28% vs 6%). Conclusions: This phase III trial of eribulin trial met its primary objective of OS benefit in pretreated pts with advanced LMS or ADI. Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. Funding Source: Eisai Inc. Clinical trial information: NCT01327885