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.

Abstract

PURPOSE:

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 AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: 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, Brian A Van Tine, Alexander Spira, Andrew Dean, Nushmia Z Khokhar, Youn Choi Park, Roland E Knoblauch, Trilok V Parekh, Robert G Maki, Shreyaskumar R Patel
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 34 Issue 8 Pg. 786-93 (Mar 10 2016) ISSN: 1527-7755 [Electronic] United States
• PMID: 26371143 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Antineoplastic Agents, Alkylating
• Dioxoles
• Tetrahydroisoquinolines
• Dacarbazine
• Trabectedin

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects)
• Dacarbazine (administration & dosage, adverse effects)
• Dioxoles (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Leiomyosarcoma (drug therapy)
• Liposarcoma (drug therapy)
• Male
• Middle Aged
• Survival Rate
• Tetrahydroisoquinolines (administration & dosage, adverse effects)
• Trabectedin
• Young Adult