TY - JOUR
T1 - Activity of eribulin mesylate in patients with soft-tissue sarcoma
T2 - A phase 2 study in four independent histological subtypes
AU - Schöffski, Patrick
AU - Ray-Coquard, Isabelle Laure
AU - Cioffi, Angela
AU - Bui, Nguyen Bin
AU - Bauer, Sebastian
AU - Hartmann, Joerg Thomas
AU - Krarup-Hansen, Anders
AU - Grünwald, Viktor
AU - Sciot, Raf
AU - Dumez, Herlinde
AU - Blay, Jean Yves
AU - Le Cesne, Axel
AU - Wanders, Jantien
AU - Hayward, Carolyn
AU - Marreaud, Sandrine
AU - Ouali, Monia
AU - Hohenberger, Peter
N1 - Funding Information:
This study was funded by Eisai Limited, Hatfield, UK. The authors acknowledge the contribution of Dorien Druyts (data management) at the European Organisation for Research and Treatment of Cancer (EORTC) Headquarters (Brussels, Belgium). The following additional investigators, not included in the author list, have entered patients into this trial: Ole Steen Nielsen (Aarhus University Hospital, Aarhus, Denmark), Piotr Rutkowski (Marie-Curie Cancer Center, Warsaw, Poland), Florence Duffaud (Centre Hospitalier Universitaire La Timone, Marseille, France), Thierry Gil (Institut Jules Bordet, Brussels, Belgium), Gunnar Folprecht (Universität Carl Gustav Carus, Dresden, Germany).
PY - 2011/10/1
Y1 - 2011/10/1
N2 - Background: Eribulin inhibits microtubule dynamics via a mechanism distinct from that of other tubulin-targeting drugs, inducing cell-cycle arrest and tumour regression in preclinical models. We assessed the activity and safety of eribulin in four strata of patients with different types of soft-tissue sarcoma. Methods: In this non-randomised multicentre phase 2 study, patients were included if they had progressive or high-grade soft-tissue sarcoma and had received no more than one previous combination chemotherapy or up to two single drugs for advanced disease. They were stratified by the type of soft-tissue sarcoma they had. Eribulin was given intravenously at a concentration of 1·4 mg/m 2 over 2-5 min at days 1 and 8 every 3 weeks to primarily assess progression-free survival at 12 weeks (RECIST 1.0), which we evaluated in all patients who started treatment. Safety analyses were done in all patients who started treatment. This trial is registered at ClinicalTrials.gov, number NCT00413192. Findings: Of 128 patients included, 37 had adipocytic sarcoma, 40 had leiomyosarcoma, 19 had synovial sarcoma, and 32 had other sarcomas. 12 (31·6%) of 38 patients with leiomyosarcoma evaluable for the primary endpoint, 15 (46·9%) of 32 patients with adipocytic sarcoma, four (21·1%) of 19 with synovial sarcoma, and five (19·2%) of 26 in other sarcomas were progression-free at 12 weeks. The most common grade 3-4 adverse events were neutropenia (66 [52%] of 127 patients evaluable for safety), leucopenia (44 [35%]), anaemia (nine [7%]), fatigue (nine [7%]), febrile neutropenia (eight [6%]), abnormal alanine aminotransferase concentrations (six [5%]), mucositis (four [3%]), and sensory neuropathy (four [3%]). Interpretation: Eribulin deserves further study in this setting, based on progression-free survival at 12 weeks in leiomyosarcoma and adipocytic sarcoma. Funding: Eisai Limited, Hatfield, UK.
AB - Background: Eribulin inhibits microtubule dynamics via a mechanism distinct from that of other tubulin-targeting drugs, inducing cell-cycle arrest and tumour regression in preclinical models. We assessed the activity and safety of eribulin in four strata of patients with different types of soft-tissue sarcoma. Methods: In this non-randomised multicentre phase 2 study, patients were included if they had progressive or high-grade soft-tissue sarcoma and had received no more than one previous combination chemotherapy or up to two single drugs for advanced disease. They were stratified by the type of soft-tissue sarcoma they had. Eribulin was given intravenously at a concentration of 1·4 mg/m 2 over 2-5 min at days 1 and 8 every 3 weeks to primarily assess progression-free survival at 12 weeks (RECIST 1.0), which we evaluated in all patients who started treatment. Safety analyses were done in all patients who started treatment. This trial is registered at ClinicalTrials.gov, number NCT00413192. Findings: Of 128 patients included, 37 had adipocytic sarcoma, 40 had leiomyosarcoma, 19 had synovial sarcoma, and 32 had other sarcomas. 12 (31·6%) of 38 patients with leiomyosarcoma evaluable for the primary endpoint, 15 (46·9%) of 32 patients with adipocytic sarcoma, four (21·1%) of 19 with synovial sarcoma, and five (19·2%) of 26 in other sarcomas were progression-free at 12 weeks. The most common grade 3-4 adverse events were neutropenia (66 [52%] of 127 patients evaluable for safety), leucopenia (44 [35%]), anaemia (nine [7%]), fatigue (nine [7%]), febrile neutropenia (eight [6%]), abnormal alanine aminotransferase concentrations (six [5%]), mucositis (four [3%]), and sensory neuropathy (four [3%]). Interpretation: Eribulin deserves further study in this setting, based on progression-free survival at 12 weeks in leiomyosarcoma and adipocytic sarcoma. Funding: Eisai Limited, Hatfield, UK.
UR - http://www.scopus.com/inward/record.url?scp=80053383254&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(11)70230-3
DO - 10.1016/S1470-2045(11)70230-3
M3 - Article
C2 - 21937277
AN - SCOPUS:80053383254
SN - 1470-2045
VL - 12
SP - 1045
EP - 1052
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 11
ER -