Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
Ann Oncol. 2014 Jun;25(6):1152-8. doi: 10.1093/annonc/mdu134. Epub 2014 Apr 1.
Breast cancer is a heterogeneous disease defined by both germline and somatic abnormalities. In preclinical models, tumors carrying homologous recombination defects are highly sensitive to trabectedin. This phase II trial evaluated the efficacy and safety of trabectedin in BRCA1/2 germline mutation carriers with pretreated metastatic breast cancer (MBC).
Trabectedin 1.3 mg/m(2) as a 3-h i.v. infusion was administered every 3 weeks until progression or intolerance. The primary efficacy end point was the objective response rate (ORR) as per RECIST. Secondary efficacy end points comprised time-to-event end points, and changes in tumor volume and expression of tumor marker CA15.3. Safety was evaluated using the NCI-CTCAE.
Forty BRCA1/2 germline mutation carriers with MBC were included. Confirmed partial response (PR) occurred in 6 of 35 assessable patients [ORR = 17%; 95% confidence interval (CI) 7% to 34%] and lasted 1.4-6.8 months. Median PFS was 3.9 months (95% CI 1.6-5.5 months). Eight patients (21%) showed changes in tumor volume, and 14 (40%) a clinical benefit. Trabectedin-related adverse events were generally mild/moderate, the most common being fatigue, nausea, constipation and anorexia. Severe laboratory abnormalities (neutropenia, transaminase increases) were mostly transient and noncumulative, and were managed by dose adjustments.
With the caveat of the limited patient number, trabectedin monotherapy showed activity and was well tolerated in heavily pretreated MBC patients selected for germline BRCA mutation. These results prompt further evaluation of trabectedin alone or combined with other specific drugs in this indication.
NCT00580112.
乳腺癌是一种由种系和体细胞异常定义的异质性疾病。在临床前模型中，携带同源重组缺陷的肿瘤对 trabectedin 高度敏感。这项 II 期试验评估了 trabectedin 治疗预处理转移性乳腺癌（MBC）的 BRCA1/2 种系突变携带者的疗效和安全性。
trabectedin 1.3mg/m² 作为 3 小时静脉输注，每 3 周给药一次，直至进展或不耐受。主要疗效终点是根据 RECIST 评估的客观缓解率（ORR）。次要疗效终点包括时间事件终点，以及肿瘤体积和肿瘤标志物 CA15.3 的表达变化。使用 NCI-CTCAE 评估安全性。
40 名 BRCA1/2 种系突变携带者的 MBC 纳入研究。35 名可评估患者中有 6 名（ORR=17%；95%CI7%至 34%）确认部分缓解（PR），持续时间为 1.4-6.8 个月。中位无进展生存期（PFS）为 3.9 个月（95%CI1.6-5.5 个月）。8 名患者（21%）的肿瘤体积发生变化，14 名（40%）有临床获益。trabectedin 相关不良事件通常为轻度/中度，最常见的是疲劳、恶心、便秘和厌食。严重的实验室异常（中性粒细胞减少、转氨酶升高）大多是短暂和非累积的，通过剂量调整来管理。
尽管患者人数有限，但 trabectedin 单药治疗在选择种系 BRCA 突变的预处理 MBC 患者中显示出活性，且耐受性良好。这些结果促使我们进一步评估 trabectedin 单独或与其他特定药物联合用于该适应证。
临床试验.gov：NCT00580112。
