title: Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial.
abstract: BACKGROUND
  A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft-tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control).
  
  
  METHODS
  We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1·4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue.
  
  
  RESULTS
  Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13·5 months [95% CI 10·9-15·6] vs 11·5 months [9·6-13·0]; hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators.
  
  
  CONCLUSIONS
  Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma.
  
  
  BACKGROUND
  Eisai.
authors.affiliation: Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: patrick.schoffski@uzleuven.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.affiliation: Sarcoma Oncology Center, Santa Monica, CA, USA.
authors.forename: Sant
authors.initials: S
authors.lastname: Chawla
authors.affiliation: Tisch Cancer Institute, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Maki
authors.affiliation: Department of Oncology, Institut Bergonié, Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
authors.affiliation: Department of Medical Oncology, Fondazione del Piemonte per I'Oncologia IRCCS, Candiolo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grignani
authors.affiliation: Department of Medical Oncology, Hospital Sírio-Libanês and Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
authors.forename: Veridiana
authors.initials: V
authors.lastname: Camargo
authors.affiliation: West German Cancer Center, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.affiliation: Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Université Claude Bernard Lyon I, LYRIC INCa-DGOS 4664 & Centre Léon Bérard, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Division of Surgical Oncology & Thoracic Surgery, Department of Surgery, Mannheim University Medical Center, Mannheim, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
authors.affiliation: Eisai, Woodcliff Lake, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: D'Adamo
authors.affiliation: Eisai, Woodcliff Lake, NJ, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Hematology, UCLA Jonsson Comprehensive Cancer, Los Angeles, CA, USA.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.affiliation: Gustave Roussy, Villejuif, France.
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.affiliation: Sarcoma Center, Dana-Farber Cancer Institute and Ludwig Center at Harvard Medical School, Boston, MA, USA.
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.affiliation: Department of Sarcoma Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shreyaskumar R
authors.initials: SR
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008080:Liposarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D005663:Furans; D007659:Ketones; C490954:eribulin; D000095662:Polyether Polyketides