A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

被引:53
作者
Bui-Nguyen, B. [1 ]
Butrynski, J. E. [2 ]
Penel, N. [3 ]
Blay, J. Y. [4 ,5 ]
Isambert, N. [6 ]
Milhem, M. [7 ]
Kerst, J. M. [8 ]
Reyners, A. K. L. [9 ]
Litiere, S. [10 ]
Marreaud, S. [10 ]
Collin, F. [6 ]
van der Graaf, W. T. A. [11 ]
机构
[1] Inst Bergonie, Ctr Comprehens Canc, Dept Med Oncol, F-33076 Bordeaux, France
[2] Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Ctr Oscar Lambret, F-59020 Lille, France
[4] Univ Lyon 1, F-69365 Lyon, France
[5] Ctr Leon Berard, F-69373 Lyon, France
[6] Ctr GF Leclerc, F-21079 Dijon, France
[7] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA
[8] Antoni van Leeuwenhoek Ziekenhuis, Netherlands Canc Inst NKI, Amsterdam, Netherlands
[9] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands
[10] EORTC Headquarters, Brussels, Belgium
[11] Radboud Univ Nijmegen, Med Ctr Nijmegen, NL-6525 ED Nijmegen, Netherlands
关键词
Soft-tissue sarcoma; Metastatic; Clinical trial; Trabectedin; Doxorubicin; First line chemotherapy; ECTEINASCIDIN-743; CHEMOTHERAPY; LIPOSARCOMA; SAFETY; ET-743;
D O I
10.1016/j.ejca.2015.03.023
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion) in terms of safety, convenience and efficacy. Patients and methods: In this randomised multicentre prospective dose-selection phase IIb superiority trial, 133 patients were randomised between doxorubicin (n = 43), trabectedin (3-hour infusion, T3h) (n = 47) and trabectedin (24-hour infusion, T24h) (n = 43). PFS was defined as time from random assignment until objective progression by response evaluation criteria in solid tumours (RECIST 1.1), a global deterioration of the health status requiring discontinuation of the treatment, or death from any cause. Results: The study was terminated due to lack of superiority in both trabectedin treatment arms as compared to the doxorubicin control arm. Median PFS was 2.8 months in the T3h arm, 3.1 months in the T24h arm and 5.5 months in the doxorubicin arm. No significant improvements in PFS were observed in the trabectedin arms as compared to the doxorubicin arm (T24h versus doxorubicin: hazard ratio (HR) 1.13, 95% confidence interval (CI) 0.67-1.90, P = .675; T3h versus doxorubicin: HR 1.50, 95% CI 0.91-2.48, P = .944). Only one toxic death occurred in the T3h arm, but treatment had to be stopped due to toxicity in 7 (15.2%) (T3h), 8 (19.5%) (T24h) and 1 (2.5%) doxorubicin patients. Conclusion: Doxorubicin continues to be the standard treatment in eligible patients with advanced/metastatic soft-tissue sarcoma (STS). Trabectedin 1.5 mg/m(2)/24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic STS. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1312 / 1320
页数:9
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