Centre Léon Bérard, Lyon, France.
The Christie NHS Foundation Trust, Manchester, United Kingdom.
Eur J Cancer. 2014 Apr;50(6):1137-47. doi: 10.1016/j.ejca.2014.01.012. Epub 2014 Feb 7.
This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS).
Patients were randomly assigned (1:1) to receive trabectedin 1.5mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v., q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6-9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point.
One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p=0.9573; hazard ratio=0.86, p=0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm.
Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.
本随机 III 期临床试验评估了一线药物 trabectedin 与基于多柔比星的化疗（DXCT）在晚期/转移性转位相关性肉瘤（TRS）患者中的疗效。
患者按 1:1 比例随机分配（随机分组），分别接受 trabectedin 1.5mg/m2 24 小时静脉输注（iv），每 3 周（q3wk）一次（A 组），或多柔比星 75mg/m2 iv，q3wk，或多柔比星 60mg/m2 iv 加异环磷酰胺（范围，6-9g/m2）iv，q3wk（B 组）。独立评估的无进展生存期（PFS）是主要疗效终点。
共 121 例患者随机分组，其中 88 例患者经中心病理复查证实为 TRS（疗效人群）。29 例 PFS 事件由独立审查评估（16 例接受 trabectedin 治疗，13 例接受 DXCT 治疗）。独立审查分析显示，两组间 PFS 无显著差异（分层对数秩检验，p=0.9573；风险比=0.86，p=0.6992）。在本分析时，trabectedin 和 DXCT 组的患者分别有 63.9%和 58.3%存活。两组间生存曲线无统计学差异。根据实体瘤反应评估标准（RECIST）v.1.0，DXCT 组的缓解率显著更高（27.0%比 5.9%），但根据 Choi 标准，两组间的反应差异较小（45.9%比 37.3%）。两组的安全性特征与预期相符，DXCT 组的严重中性粒细胞减少症、脱发和黏膜炎发生率较高。
在晚期转位相关性肉瘤患者的一线治疗中，trabectedin 和基于多柔比星的化疗均未显示出显著优势。
