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

• Published in: European journal of cancer (1990) 2014-04, Vol.50 (6), p.1137-1147
• Main Authors: Blay, Jean-Yves, Leahy, Michael G, Nguyen, Binh Bui, Patel, Shreyaskumar R, Hohenberger, Peter, Santoro, Armando, Staddon, Arthur P, Penel, Nicolas, Piperno-Neumann, Sophie, Hendifar, Andrew, Lardelli, Pilar, Nieto, Antonio, Alfaro, Vicente, Chawla, Sant P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anemia - chemically induced; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Dioxoles - adverse effects; Dioxoles - therapeutic use; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Drug Administration Schedule; Fatigue - chemically induced; Female; Hematology, Oncology and Palliative Medicine; Humans; Ifosfamide - administration & dosage; Ifosfamide - adverse effects; Kaplan-Meier Estimate; Leukopenia - chemically induced; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nausea - chemically induced; Pharmacology. Drug treatments; Sarcoma - drug therapy; Sarcoma - genetics; Sarcomas; Tetrahydroisoquinolines - adverse effects; Tetrahydroisoquinolines - therapeutic use; Trabectedin; Translocation; Translocation, Genetic; Treatment Outcome; Tumors; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2014.01.012

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 1.5 mg/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.