Breast Medical Oncology, The Cancer Institute Hospital Ariake of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan; Breast Oncology Center, The Cancer Institute Hospital Ariake of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Breast Medical Oncology, The Cancer Institute Hospital Ariake of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan; Breast Oncology Center, The Cancer Institute Hospital Ariake of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Breast. 2017 Oct;35:78-84. doi: 10.1016/j.breast.2017.06.015. Epub 2017 Jun 27.
The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients.
In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab. The pharmacokinetics of eribulin in this combination were assessed in 6 patients. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary endpoint was objective response rate (ORR).
A total of 30 patients (median age, 58 years; range, 31-76) were enrolled, with a median number of previous chemotherapy regimens of 3.5 (range: 1-9) in the metastatic setting. Pharmacokinetic parameters of eribulin in this combination were similar to previous reports of eribulin monotherapy. ORR was 34.8% (95% CI: 16.4-57.3, n = 23), and median progression-free survival was 42.6 weeks (95% CI: 20.3-51.9, n = 30). Clinical benefit rate was 60.9% (95% CI: 16.4-57.3). The most common grade 3/4 adverse event was neutropenia in 20 patients (66.7%). A dose reduction of eribulin was required in 27 patients due to adverse events, particularly grade 3 neutropenia.
Eribulin in combination with pertuzumab and trastuzumab was well tolerated in heavily pretreated patients. Eribulin may be a viable treatment option when used in combination with pertuzumab and trastuzumab for HER2-positive ABC patients (UMIN Clinical Trial Registry identification number, UMIN000012375).
在晚期乳腺癌（ABC）患者中继续使用多种抗 HER2 治疗的疗效和安全性尚不清楚。本研究调查了艾立布林联合培妥珠单抗和曲妥珠单抗用于紫杉烷和曲妥珠单抗预处理过的 HER2 阳性 ABC 患者。
在一项单机构、单臂、开放标签、II 期试验中，先前接受过紫杉烷和曲妥珠单抗治疗的 HER2 阳性 ABC 患者接受艾立布林联合培妥珠单抗和曲妥珠单抗治疗。在 6 例患者中评估了艾立布林联合用药的药代动力学。在前 6 个周期每 6 周进行一次肿瘤评估，此后每 12 周进行一次。主要终点是客观缓解率（ORR）。
共纳入 30 例患者（中位年龄 58 岁；范围 31-76 岁），转移性疾病中先前化疗方案的中位数为 3.5 个（范围：1-9 个）。该联合用药的艾立布林药代动力学参数与艾立布林单药治疗的先前报告相似。ORR 为 34.8%（95%CI：16.4-57.3，n=23），中位无进展生存期为 42.6 周（95%CI：20.3-51.9，n=30）。临床获益率为 60.9%（95%CI：16.4-57.3）。最常见的 3/4 级不良事件是 20 例患者（66.7%）的中性粒细胞减少症。由于不良事件，特别是 3 级中性粒细胞减少症，27 例患者需要减少艾立布林剂量。
在预处理过的患者中，艾立布林联合培妥珠单抗和曲妥珠单抗耐受性良好。当艾立布林联合培妥珠单抗和曲妥珠单抗用于 HER2 阳性 ABC 患者时，艾立布林可能是一种可行的治疗选择（UMIN 临床试验注册编号，UMIN000012375）。
