University of Arizona Cancer Center, 3838 N Campbell Ave, Tucson, AZ, 85719, USA.
College of Medicine, University of Arizona, Tucson, AZ, USA.
Breast Cancer Res Treat. 2021 Jul;188(1):91-99. doi: 10.1007/s10549-021-06175-x. Epub 2021 Apr 2.
Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician's choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile.
We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy.
We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients.
Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.
转移性乳腺癌（MBC）对蒽环类药物和紫杉烷类药物耐药的治疗选择有限。在一项 III 期试验中，与医生选择的治疗相比，艾立布林显著改善了总生存期，但由于中性粒细胞减少和周围神经病变，其耐受性有限。基于其他疗法替代治疗方案的先前研究，我们假设艾立布林的低剂量节拍方案将允许患者更一致地继续治疗而不会出现治疗延迟，从而延长进展时间，并改善毒性特征。
我们进行了一项多中心、单臂、II 期临床试验，入组了 MBC 患者。所有患者均接受节拍式艾立布林（0.9mg/m 静脉注射，第 1、8 和 15 天，每 28 天为一个周期）治疗。治疗继续进行，直到患者出现疾病进展、无法耐受的毒性或选择停止研究。患者必须有先前的紫杉烷类药物暴露。主要终点是无进展生存期。次要终点是总生存期、缓解率和临床获益率。进行了探索性生物标志物分析，以分析循环内皮细胞（CEC）、循环内皮前体细胞和碳酸酐酶 IX（CAIX）水平的变化与治疗反应的关系。
我们同意入组 86 例患者，最终有 59 例可进行最终分析。中位年龄为 59 岁；78%的患者肿瘤 HER2 阴性。中位无进展生存期（PFS）为 3.5 个月，总生存期（OS）为 14.3 个月。客观缓解率为 15%，临床获益率为 48%。报告的 3 级中性粒细胞减少和周围神经病变分别为 18%和 5%。因毒性而停止治疗的患者占 3%。
节拍式每周低剂量艾立布林是一种有效且耐受良好的方案，与批准剂量和方案相比，骨髓抑制、脱发和周围神经病变明显减少，允许更长的使用时间和疾病控制，与标准剂量方案相比具有相似的结果。
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