基于艾立布林的新辅助化疗在同源重组缺陷状态分层的三阴性乳腺癌患者中的应用：一项多中心随机 II 期临床试验。
Eribulin-based neoadjuvant chemotherapy for triple-negative breast cancer patients stratified by homologous recombination deficiency status: a multicenter randomized phase II clinical trial.
机构信息
Department of Surgery, Breast Oncology, NHO Osaka National Hospital, 2-1-14 Hoenzaka, Chuou-ku, Osaka, Japan.
Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
出版信息
Breast Cancer Res Treat. 2021 Jul;188(1):117-131. doi: 10.1007/s10549-021-06184-w. Epub 2021 Mar 25.
PURPOSE
To investigate clinical usefulness of eribulin-based neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) patients.
METHODS
Patients in group A (aged < 65 years with homologous recombination deficiency, HRD, score ≥ 42, or those at any age with germline BRCA mutation, gBRCAm) were randomized to 4 cycles of paclitaxel plus carboplatin (group A1) or eribulin plus carboplatin (group A2), followed by 4 cycles of anthracycline. Patients in group B (aged < 65 years with HRD score < 42, or aged ≥ 65 years without gBRCAm) were randomized to 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2); non-responders to the first 4 cycles of the eribulin-based therapy received anthracycline. Primary endpoint was pCR rate (ypT0-is, ypN0; centrally confirmed). Main secondary endpoint was safety.
RESULTS
The full analysis set comprised 99 patients. The pCR rate was 65% (90% CI, 46%-81%) and 45% (27%-65%) in groups A1 and A2, respectively, and 19% (8%-35%) in both groups B1 and B2. No major difference was seen in secondary endpoints, but peripheral neuropathy incidence was 74% in group A1, whereas it was 32%, 22%, and 26% in groups A2, B1, and B2, respectively.
CONCLUSIONS
In patients aged < 65 years with high HRD score or gBRCAm, weekly paclitaxel plus carboplatin and eribulin plus carboplatin followed by anthracycline resulted in a pCR rate of > 60% and > 40%, respectively, suggesting potential usefulness of patient stratification using HRD; pCR tended to be low in patients with HRD-negative tumors. Neurotoxicity was less frequent with the eribulin-based regimen.
TRIAL REGISTRATION
The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.
目的
研究表柔比星联合环磷酰胺序贯多西他赛与白蛋白紫杉醇联合卡铂新辅助化疗治疗局部晚期三阴性乳腺癌的疗效。
方法
选择 2010 年 1 月至 2017 年 12 月期间在我院接受新辅助化疗的局部晚期三阴性乳腺癌患者 99 例，根据化疗方案不同分为两组：A 组（年龄<65 岁且同源重组修复缺陷评分（HRD）≥42 分或任何年龄伴胚系 BRCA 基因突变（gBRCAm）患者）：接受紫杉醇联合卡铂（A1 组）或表柔比星联合卡铂（A2 组）治疗 4 个周期，序贯蒽环类药物 4 个周期；B 组（年龄<65 岁且 HRD<42 分或年龄≥65 岁且不伴 gBRCAm 患者）：接受表柔比星联合环磷酰胺（B1 组）或表柔比星联合卡培他滨（B2 组）治疗 6 个周期，对前 4 周期表柔比星为基础的方案无反应的患者接受蒽环类药物治疗。主要终点为ypT0-is、ypN0（中心确认）的病理完全缓解率（pCR）。主要次要终点为安全性。
结果
99 例患者均完成了分析。A1 组和 A2 组的 pCR 率分别为 65%（90%CI，46%-81%）和 45%（27%-65%），B1 组和 B2 组的 pCR 率分别为 19%（8%-35%）。次要终点无显著差异，但 A1 组的周围神经病变发生率为 74%，而 A2 组、B1 组和 B2 组的发生率分别为 32%、22%和 26%。
结论
对于 HRD 评分高或伴 gBRCAm 的<65 岁患者，每周紫杉醇联合卡铂和表柔比星联合卡铂序贯蒽环类药物化疗后 pCR 率分别>60%和>40%，提示 HRD 患者分层具有潜在的应用价值；HRD 阴性肿瘤的 pCR 率较低。基于表柔比星的方案神经毒性较少。
试验注册
本研究已在大学医院医疗信息网络临床试验注册中心（http://www.umin.ac.jp/ctr/index-j.htm）注册，注册号为 UMIN000023162。日本乳腺癌研究组的试验编号为 JBCRG-22。
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