Phase 2 Study of Trabectedin in Patients With Hormone Receptor-Positive, HER-2-Negative, Advanced Breast Carcinoma According to Expression of Xeroderma Pigmentosum G Gene
Phase 2 Study of Trabectedin in Patients With Hormone Receptor-Positive, HER-2-Negative, Advanced Breast Carcinoma According to Expression of Xeroderma Pigmentosum G Gene
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DOI：
10.1016/j.clbc.2016.05.005
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发表时间：
2016-10-01
影响因子：
3.1
通讯作者：
Delaloge, Suzette
中科院分区：
文献类型：
--
作者：
Awada, Ahmad;Cortes, Javier;Delaloge, Suzette
背景：临床前和临床数据表明着色性干皮病G基因（XPG）状态可能预测曲贝替定的疗效。这项II期研究根据XPG mRNA表达的肿瘤水平，评价了曲贝替定以1.3 mg/m2的剂量每3周一次静脉输注3小时在激素受体阳性、HER-2（人表皮生长因子受体2）阴性的晚期乳腺癌患者中的疗效。患者和方法：将患者分层为高XPG（>3）或低XPG（6例患者经历PFS 4），因此不符合要求，停止招募。1例高XPG患者出现部分缓解（ORR，5%）。1例低XPG患者完全缓解，2例低XPG患者部分缓解（ORR，13%）。高XPG和低XPG患者之间的疗效参数比较显示无统计学显著差异。疗效人群的ORR为9.3%，中位PFS为1.9个月，总生存期为11.8个月。trabectedin在乳腺癌中的安全性与其他适应症相似。结论：曲贝替定单药治疗HER-2阴性、HER-2阳性的晚期乳腺癌疗效有限。XPG mRNA表达不能预测曲贝替丁的疗效。
Background: Preclinical and clinical data suggest that xeroderma pigmentosum G gene (XPG) status might predict trabectedin efficacy. This phase 2 study evaluated the efficacy of trabectedin at a dose of 1.3 mg/m2 as a 3-hour intravenous infusion every 3 weeks in hormone receptor-positive, HER-2 (human epidermal growth factor receptor 2)-negative, advanced breast cancer patients according to the tumor level of XPG mRNA expression. Patients and Methods: Patients were stratified into high-XPG (>3) or low-XPG ( 6 patients experienced PFS4) was thus not met, and recruitment was stopped. One high-XPG patient had a partial response (ORR, 5%). One low-XPG patient had a complete response, and 2 low-XPG patients had partial responses (ORR, 13%). Comparison of efficacy parameters between high-XPG and low-XPG patients showed no statistically significant differences. ORR in the efficacy population was 9.3%, median PFS was 1.9 months, and overall survival was 11.8 months. The safety of trabectedin in breast carcinoma was similar to that shown in other indications. Conclusion: Trabectedin as single agent had limited activity in hormone-positive, HER-2enegative advanced breast cancer. XPG mRNA expression was not predictive of trabectedin efficacy.