title: Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas.
abstract: OBJECTIVE
  This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS).
  
  
  METHODS
  Patients were randomly assigned (1:1) to receive trabectedin 1.5mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v., q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6-9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point.
  
  
  RESULTS
  One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p=0.9573; hazard ratio=0.86, p=0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm.
  
  
  CONCLUSIONS
  Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.
authors: Centre Léon Bérard, Lyon, France. Electronic address: jean-yves.blay@lyon.unicancer.fr.
authors: Jean-Yves
authors: JY
authors: Blay
authors: The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors: Michael G
authors: MG
authors: Leahy
authors: Institut Bergonie, Bordeaux, France.
authors: Binh Bui
authors: BB
authors: Nguyen
authors: University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Shreyaskumar R
authors: SR
authors: Patel
authors: Universitätsklinikum Mannheim, Mannheim, Germany.
authors: Peter
authors: P
authors: Hohenberger
authors: Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS, Rozzano, Italy.
authors: Armando
authors: A
authors: Santoro
authors: Joan Karnell Cancer Center, Pennsylvania Hospital, PA, USA.
authors: Arthur P
authors: AP
authors: Staddon
authors: Centre Oscar Lambret, Lille, France.
authors: Nicolas
authors: N
authors: Penel
authors: Institut Curie, Paris, France.
authors: Sophie
authors: S
authors: Piperno-Neumann
authors: Sarcoma Oncology Center, Santa Monica, CA, USA.
authors: Andrew
authors: A
authors: Hendifar
authors: PharmaMar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors: Pilar
authors: P
authors: Lardelli
authors: PharmaMar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors: Antonio
authors: A
authors: Nieto
authors: PharmaMar, Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors: Vicente
authors: V
authors: Alfaro
authors: Sarcoma Oncology Center, Santa Monica, CA, USA.
authors: Sant P
authors: SP
authors: Chawla
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin; D014178:Translocation, Genetic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D004317:Doxorubicin; D000077606:Trabectedin; D007069:Ifosfamide
keywords: Chemotherapy; Sarcomas; Trabectedin; Translocation