Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Internal Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
JAMA Oncol. 2021 Jul 1;7(7):978-984. doi: 10.1001/jamaoncol.2021.1371.
Primary analysis of the TRAIN-2 study showed high pathologic complete response rates after neoadjuvant chemotherapy with or without anthracyclines plus dual ERBB2 (formerly HER2) blockade.
To evaluate 3-year event-free survival (EFS) and overall survival (OS) of an anthracycline-free and anthracycline-containing regimen with dual ERBB2 blockade in patients with stage II and III ERBB2-positive breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: A total of 438 patients with stage II and III ERBB2-positive breast cancer were enrolled in this randomized, clinical, open-label phase 3 trial across 37 hospitals in the Netherlands from December 9, 2013, until January 14, 2016. Follow-up analyses were performed after a median follow-up of 48.8 months (interquartile range, 44.1-55.2 months). Analysis was performed on an intention-to-treat basis.
Participants were randomly assigned on a 1:1 basis, stratified by age, tumor stage, nodal stage, and estrogen receptor status, to receive 3 cycles of fluorouracil (500 mg/m2), epirubicin (90 mg/m2), and cyclophosphamide (500 mg/m2), followed by 6 cycles of paclitaxel and carboplatin or 9 cycles of paclitaxel (80 mg/m2 days 1 and 8) and carboplatin (area under the concentration-time curve, 6 mg/mL/min). Both groups received trastuzumab (6 mg/kg; loading dose 8 mg/kg) and pertuzumab (420 mg intravenously; loading dose 840 mg) every 3 weeks.
Three-year EFS, OS, and safety.
A total of 438 women were randomized, with 219 per group (anthracycline group, median age, 49 years [interquartile range, 43-55 years]; and nonanthracycline group, median age, 48 years [interquartile range, 43-56 years]). A total of 23 EFS events (10.5%) occurred in the anthracycline group and 21 EFS events (9.6%) occurred in the nonanthracycline group (hazard ratio, 0.90; 95% CI, 0.50-1.63; favoring nonanthracyclines). Three-year EFS estimates were 92.7% (95% CI, 89.3%-96.2%) in the anthracycline group and 93.6% (95% CI, 90.4%-96.9%) in the nonanthracycline group and 3-year OS estimates were 97.7% (95% CI, 95.7%-99.7%) in the anthracycline group and 98.2% (95% CI, 96.4%-100%) in the nonanthracycline group. The results were irrespective of hormone receptor and nodal status. A decline in left ventricular ejection fraction of 10% or more from baseline to less than 50% was more common in patients who received anthracyclines than those who did not (17 of 220 [7.7%] vs 7 of 218 [3.2%]; P = .04). Two patients treated with anthracyclines developed acute leukemia.
This follow-up analysis of the TRAIN-2 study shows similar 3-year EFS and OS estimates with or without anthracyclines in patients with stage II and III ERBB2-positive breast cancer. Anthracycline use is associated with increased risk of febrile neutropenia, cardiotoxic effects, and secondary malignant neoplasms.
ClinicalTrials.gov Identifier: NCT01996267.
TRAIN-2 研究的主要分析显示，新辅助化疗联合或不联合蒽环类药物加双 ERBB2（以前称为 HER2）阻断治疗后，病理完全缓解率较高。
评估无蒽环类药物和含蒽环类药物的双 ERBB2 阻断方案在 II 期和 III 期 ERBB2 阳性乳腺癌患者中的 3 年无事件生存（EFS）和总生存（OS）。
设计、地点和参与者：共有 438 名 II 期和 III 期 ERBB2 阳性乳腺癌患者于 2013 年 12 月 9 日至 2016 年 1 月 14 日在荷兰的 37 家医院参与了这项随机、临床、开放标签的 3 期试验。中位随访 48.8 个月（四分位距，44.1-55.2 个月）后进行了随访分析。分析基于意向治疗原则。
参与者按照 1:1 的比例随机分配，按年龄、肿瘤分期、淋巴结分期和雌激素受体状态分层，接受 3 个周期的氟尿嘧啶（500 mg/m2）、表柔比星（90 mg/m2）和环磷酰胺（500 mg/m2），随后接受 6 个周期的紫杉醇和卡铂或 9 个周期的紫杉醇（80 mg/m2，第 1 天和第 8 天）和卡铂（浓度时间曲线下面积，6 mg/mL/min）。两组均接受曲妥珠单抗（6 mg/kg；负荷剂量 8 mg/kg）和帕妥珠单抗（420 mg 静脉注射；负荷剂量 840 mg）每 3 周一次。
3 年 EFS、OS 和安全性。
共有 438 名女性被随机分组，每组 219 名（蒽环类药物组，中位年龄 49 岁[四分位距，43-55 岁]；非蒽环类药物组，中位年龄 48 岁[四分位距，43-56 岁]）。蒽环类药物组发生 23 例 EFS 事件（10.5%），非蒽环类药物组发生 21 例 EFS 事件（9.6%）（风险比，0.90；95%CI，0.50-1.63；有利于非蒽环类药物）。蒽环类药物组 3 年 EFS 估计值为 92.7%（95%CI，89.3%-96.2%），非蒽环类药物组为 93.6%（95%CI，90.4%-96.9%）；蒽环类药物组 3 年 OS 估计值为 97.7%（95%CI，95.7%-99.7%），非蒽环类药物组为 98.2%（95%CI，96.4%-100%）。结果与激素受体和淋巴结状态无关。蒽环类药物组较非蒽环类药物组更常见左心室射血分数从基线下降 10%或更多至低于 50%（17/220 [7.7%] vs 7/218 [3.2%]；P = .04）。2 例接受蒽环类药物治疗的患者发生急性白血病。
TRAIN-2 研究的随访分析显示，在 II 期和 III 期 ERBB2 阳性乳腺癌患者中，使用或不使用蒽环类药物联合双 ERBB2 阻断治疗的 3 年 EFS 和 OS 估计值相似。蒽环类药物的使用与发热性中性粒细胞减少症、心脏毒性作用和继发性恶性肿瘤的风险增加相关。
ClinicalTrials.gov 标识符：NCT01996267。
