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

被引：655

作者：

Demetri, George D. ^{[1
,2
]}

von Mehren, Margaret ^{[3
]}

Jones, Robin L. ^{[6
]}

Hensley, Martee L. ^{[7
]}

Schuetze, Scott M. ^{[9
]}

Staddon, Arthur ^{[4
]}

Milhem, Mohammed ^{[10
]}

Elias, Anthony ^{[11
]}

Ganjoo, Kristen ^{[12
]}

Tawbi, Hussein ^{[5
]}

Van Tine, Brian A. ^{[13
]}

Spira, Alexander ^{[14
]}

Dean, Andrew ^{[15
]}

Khokhar, Nushmia Z. ^{[16
]}

Park, Youn Choi ^{[16
]}

Knoblauch, Roland E. ^{[16
]}

Parekh, Trilok V. ^{[16
]}

Maki, Robert G. ^{[8
]}

Patel, Shreyaskumar R. ^{[17
]}

机构：

[1] Dana Farber Canc Inst, Boston, MA USA

[2] Ludwig Ctr Harvard, Boston, MA USA

[3] Fox Chase Canc Ctr, Philadelphia, PA USA

[4] Univ Penn, Philadelphia, PA 19104 USA

[5] Univ Pittsburgh, Inst Canc, Philadelphia, PA USA

[6] Seattle Canc Care Alliance, Seattle, WA USA

[7] Mem Sloan Kettering Canc Ctr, New York, NY USA

[8] Mt Sinai Med Ctr, New York, NY 10029 USA

[9] Univ Michigan, Ann Arbor, MI 48109 USA

[10] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA

[11] Univ Colorado, Ctr Canc, Aurora, CO USA

[12] Stanford Hosp & Clin, Stanford, CA USA

[13] Washington Univ, St Louis, MO USA

[14] Virginia Canc Specialists, Fairfax, VA USA

[15] St John God Hosp, Bendat Canc Ctr, Subiaco, WA, Australia

[16] Janssen Res & Dev, Raritan, NJ USA

[17] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2016年 / 34卷 / 08期

关键词：

SOFT-TISSUE SARCOMAS; DOXORUBICIN PLUS IFOSFAMIDE; EUROPEAN-ORGANIZATION; 1ST-LINE TREATMENT; ECTEINASCIDIN-743; GEMCITABINE; ANTITUMOR; EORTC; PAZOPANIB; PLACEBO;

D O I：

10.1200/JCO.2015.62.4734

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2015 by American Society of Clinical Oncology

引用

页码：786 / +

页数：10

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