George D Demetri1, Margaret von Mehren2, Robin L Jones2, Martee L Hensley2, Scott M Schuetze2, Arthur Staddon2, Mohammed Milhem2, Anthony Elias2, Kristen Ganjoo2, Hussein Tawbi2, Brian A Van Tine2, Alexander Spira2, Andrew Dean2, Nushmia Z Khokhar2, Youn Choi Park2, Roland E Knoblauch2, Trilok V Parekh2, Robert G Maki2, Shreyaskumar R Patel2. 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.
RCT Entities:
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.
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