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

Autor: Shreyaskumar Patel, Jean-Yves Blay, Sebastian Bauer, Axel Le Cesne, Patrick Schöffski, Sun Young Rha, George D. Demetri, D. R. D'Adamo, Robert G. Maki, Antoine Italiano, Giovanni Grignani, Matthew Guo, Peter Hohenberger, Bartosz Chmielowski, Veridiana Pires de Camargo, Sant P. Chawla, Hans Gelderblom, Edwin Choy
Přispěvatelé: Department of General Medical Oncology [Leuven], University Hospitals Leuven [Leuven], Sarcoma Oncology Center, Sarcoma program, New York University [New York] (NYU), NYU System (NYU)-NYU System (NYU), Service de Pathologie, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Leids Universitair Medisch Centrum [Leiden, The Netherlands], Universität Duisburg-Essen [Essen], Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], New York University [New York], Institut Bergonié, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR )
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Leiomyosarcoma
Survival
Medizin
Phases of clinical research
Soft Tissue Neoplasms
Medical Oncology
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
surgery
chemistry.chemical_compound
0302 clinical medicine
Belgium
Germany
Clinical endpoint
Aged
80 and over

education.field_of_study
Hazard ratio
Sarcoma
General Medicine
Liposarcoma
Ketones
Middle Aged
3. Good health
Dacarbazine
Treatment Outcome
Tolerability
Italy
030220 oncology & carcinogenesis
Disease Progression
Medicine
Female
France
Brazil
Eribulin
medicine.drug
Adult
medicine.medical_specialty
Patients
Population
Antineoplastic Agents
[SDV.CAN]Life Sciences [q-bio]/Cancer
methods
Young Adult
03 medical and health sciences
Internal medicine
medicine
Humans
Furans
education
Antineoplastic Agents
Alkylating

Survival analysis
Aged
business.industry
Survival Analysis
Surgery
030104 developmental biology
chemistry
Neoplasm Grading
business
Zdroj: Lancet
Lancet, Elsevier, 2016, 387 (10028), pp.1629-1637. ⟨10.1016/S0140-6736(15)01283-0⟩
Lancet, Elsevier, 2016, 387 (10028), pp.1629-1637. 〈http://linkinghub.elsevier.com/retrieve/pii/S0140673615012830〉. 〈10.1016/S0140-6736(15)01283-0〉
Lancet, 387(10028), 1629-1637
ISSN: 0140-6736
1474-547X
DOI: 10.1016/S0140-6736(15)01283-0⟩
Popis: Summary 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.
Databáze: OpenAIRE
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