Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial

Schoffski, P., Chawla, S., Maki, R. G., Italiano, A., Gelderblom, H., Choy, E., Grignani, G., Camargo, V., Bauer, S., Rha, S. Y., Blay, J. Y., Hohenberger, P., D'Adamo, D., Guo, M., Chmielowski, B., Le Cesne, A., Demetri, G. D., Patel, S. R. (April 2016) Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet, 387 (10028). pp. 1629-37. ISSN 0140-6736

URL: https://www.ncbi.nlm.nih.gov/pubmed/26874885
DOI: 10.1016/s0140-6736(15)01283-0

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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Eisai.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Aged, 80 and over Antineoplastic Agents/adverse effects/*therapeutic use Antineoplastic Agents, Alkylating/adverse effects/therapeutic use Dacarbazine/adverse effects/*therapeutic use Female Furans/adverse effects/*therapeutic use Humans Ketones/adverse effects/*therapeutic use Leiomyosarcoma/*drug therapy/pathology/secondary Liposarcoma/*drug therapy/pathology/secondary Male Middle Aged Neoplasm Grading Soft Tissue Neoplasms/*drug therapy Survival Analysis Treatment Outcome Young Adult
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 16 April 2016
Date Deposited: 06 Mar 2018 17:35
Last Modified: 06 Mar 2018 17:35
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36176

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