Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

Eur J Cancer. 2014 Apr;50(6):1137-47. doi: 10.1016/j.ejca.2014.01.012. Epub 2014 Feb 7.

Abstract

Aim: 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.

Conclusion: Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.

Trial registration: ClinicalTrials.gov NCT00796120.

Keywords: Chemotherapy; Sarcomas; Trabectedin; Translocation.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anemia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dioxoles / adverse effects
  • Dioxoles / therapeutic use*
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use*
  • Drug Administration Schedule
  • Fatigue / chemically induced
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects
  • Kaplan-Meier Estimate
  • Leukopenia / chemically induced
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Sarcoma / drug therapy*
  • Sarcoma / genetics
  • Tetrahydroisoquinolines / adverse effects
  • Tetrahydroisoquinolines / therapeutic use*
  • Trabectedin
  • Translocation, Genetic
  • Treatment Outcome
  • Young Adult

Substances

  • Dioxoles
  • Tetrahydroisoquinolines
  • Doxorubicin
  • Trabectedin
  • Ifosfamide

Associated data

  • ClinicalTrials.gov/NCT00796120