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J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.

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.

Author information

1
George D. Demetri, Dana-Farber Cancer Institute and Ludwig Center at Harvard, Boston, MA; Margaret von Mehren, Fox Chase Cancer Center; Arthur Staddon, University of Pennsylvania, Philadelphia; Hussein Tawbi, University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robin L. Jones, Seattle Cancer Care Alliance, Seattle, WA; Martee L. Hensley, Memorial Sloan Kettering Cancer Center; Robert G. Maki, Mount Sinai Medical Center, New York, NY; Scott M. Schuetze, University of Michigan, Ann Arbor, MI; Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA; Anthony Elias, University of Colorado Cancer Center, Aurora, CO; Kristen Ganjoo, Stanford Hospital and Clinics, Stanford, CA; Brian A. Van Tine, Washington University in St Louis, St Louis, MO; Alexander Spira, Virginia Cancer Specialists, Fairfax, VA; Andrew Dean, St John of God Hospital-Bendat Cancer Centre, Subiaco, Western Australia, Australia; Nushmia Z. Khokhar, Youn Choi Park, Roland E. Knoblauch, and Trilok V. Parekh, Janssen Research & Development, Raritan, NJ; and Shreyaskumar R. Patel, The University of Texas MD Anderson Cancer Center, Houston, TX. george_demetri@dfci.harvard.edu.
2
George D. Demetri, Dana-Farber Cancer Institute and Ludwig Center at Harvard, Boston, MA; Margaret von Mehren, Fox Chase Cancer Center; Arthur Staddon, University of Pennsylvania, Philadelphia; Hussein Tawbi, University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robin L. Jones, Seattle Cancer Care Alliance, Seattle, WA; Martee L. Hensley, Memorial Sloan Kettering Cancer Center; Robert G. Maki, Mount Sinai Medical Center, New York, NY; Scott M. Schuetze, University of Michigan, Ann Arbor, MI; Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA; Anthony Elias, University of Colorado Cancer Center, Aurora, CO; Kristen Ganjoo, Stanford Hospital and Clinics, Stanford, CA; Brian A. Van Tine, Washington University in St Louis, St Louis, MO; Alexander Spira, Virginia Cancer Specialists, Fairfax, VA; Andrew Dean, St John of God Hospital-Bendat Cancer Centre, Subiaco, Western Australia, Australia; Nushmia Z. Khokhar, Youn Choi Park, Roland E. Knoblauch, and Trilok V. Parekh, Janssen Research & Development, Raritan, NJ; and Shreyaskumar R. Patel, The University of Texas MD Anderson Cancer Center, Houston, TX.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01343277.

PMID:
26371143
PMCID:
PMC5070559
DOI:
10.1200/JCO.2015.62.4734
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

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