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Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial
Journal article   Open access   Peer reviewed

Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial

George D Demetri, Margaret von Mehren, Robin L Jones, Martee L Hensley, Scott M Schuetze, Arthur Staddon, Mohammed Milhem, Anthony Elias, Kristen Ganjoo, Hussein Tawbi, …
Journal of clinical oncology, Vol.34(8), pp.786-793
03/10/2016
DOI: 10.1200/JCO.2015.62.4734
PMCID: PMC5070559
PMID: 26371143
url
https://doi.org/10.1200/JCO.2015.62.4734View
Published (Version of record) Open Access

Abstract

This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient-reported symptom scoring. A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies.
Dacarbazine - administration & dosage Dacarbazine - adverse effects Dioxoles - adverse effects Drug Administration Schedule Liposarcoma - drug therapy Humans Middle Aged Male Survival Rate Tetrahydroisoquinolines - administration & dosage Tetrahydroisoquinolines - adverse effects Antineoplastic Agents, Alkylating - administration & dosage Trabectedin Young Adult Disease-Free Survival Dioxoles - administration & dosage Adolescent Aged, 80 and over Adult Female Leiomyosarcoma - drug therapy Aged Antineoplastic Agents, Alkylating - adverse effects

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