• 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, and Shreyaskumar R Patel.
• 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.
• J. Clin. Oncol. 2016 Mar 10; 34 (8): 786-93.

PurposeThis 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 MethodsPatients 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.ResultsA 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.ConclusionTrabectedin 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.© 2015 by American Society of Clinical Oncology.

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