HELEN-006 (NCT04547907): A Comparison of Nab-PHP and TCbHP Efficacy in Neoadjuvant Therapy for HER2-positive Early Breast Cancer
Brief Title: Comparing the Efficacy of Nab-PHP and TCbHP in Neoadjuvant Therapy for HER2 Positive Operable Breast Cancer
Official Title: Comparing the Efficacy and Security of Nab-PHP and TCbHP in Neoadjuvant Chemotherapy for HER2 Positive Operable Breast Cancer, A Multicenter, Randomized, Phase III Clinical Trial
白蛋白紫杉醇组332例：每21天静脉注射白蛋白紫杉醇（125mg/m²，第1、8和15天）6个周期 多西他赛卡铂组337例：每21天静脉注射多西他赛（75mg/m²，第1天）卡铂（浓度时间曲线下面积6mg/mL每分钟，第1天）6个周期
病理完全缓解：220例、194例 病理完全缓解率：66.3%比57.6%（95%置信区间：61.2～71.4、52.3～62.9） 合并优势比：1.54（95%置信区间：1.10～2.14，分层P=0.011） 3～4级不良事件发生率：30%比38% 3～4级恶心发生率：7%比23% 3～4级腹泻发生率：8%比16% 3～4级神经病变发生率：13%比2% 严重药物相关不良事件发生率：1%比2% 治疗相关死亡发生率：0比0
Lancet Oncol. 2024 Nov 26. IF: 41.6
De-escalated neoadjuvant weekly nab-paclitaxel with trastuzumab and pertuzumab versus docetaxel, carboplatin, trastuzumab, and pertuzumab in patients with HER2-positive early breast cancer (HELEN-006): a multicentre, randomised, phase 3 trial.
Xiu-Chun Chen, De-Chuang Jiao, Jiang-Hua Qiao, Cheng-Zheng Wang, Xian-Fu Sun, Zhen-Duo Lu, Lian-Fang Li, Chong-Jian Zhang, Min Yan, Ya Wei, Bo Chen, Yue-Qing Feng, Miao Deng, Ming-De Ma, Jennifer K Plichta, You-Wen He, Zhen-Zhen Liu.
The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China; Anyang Tumor Hospital, Anyang, China; The First Hospital of China Medical University, Shenyang, China; Xinxiang Central Hospital, Xinxiang, China; The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China; Huaihe Hospital of Henan University, Kaifeng, China; Duke University School of Medicine, Durham, NC, USA.
BACKGROUND: A previous phase 2 trial showed promising outcomes for patients with HER2-positive early-stage breast cancer using neoadjuvant de-escalation chemotherapy with paclitaxel, trastuzumab, and pertuzumab. We aimed to evaluate the efficacy of weekly nab-paclitaxel compared with the standard regimen of docetaxel plus carboplatin, both with trastuzumab and pertuzumab, as neoadjuvant therapies for patients with HER2-positive breast cancer.
METHODS: HELEN-006 was a multicentre, randomised, phase 3 trial done at six hospitals in China. We enrolled patients aged 18-70 years with untreated, histologically confirmed stage II-III invasive HER2-positive breast cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1. Using an interactive response system, patients were randomly assigned (1:1) under a permuted block randomisation scheme (block size of four), stratified by tumour stage, nodal status, and hormone receptor status. Patients received either intravenous nab-paclitaxel (125 mg/m2 on days 1, 8, and 15) for six 3-week cycles, or intravenous docetaxel (75 mg/m2 on day 1) plus intravenous carboplatin (area under the concentration-time curve 6 mg/mL per min on day 1) for six 3-week cycles. Both groups also received concurrent intravenous trastuzumab, with an initial loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg on day 1, as well as intravenous pertuzumab with a loading dose of 840 mg and a maintenance dose of 420 mg on day 1. This report is the final analysis of the primary endpoint, pathological complete response (ypT0/is ypN0), analysed in all patients who started treatment (modified intention to treat). The trial is registered with ClinicalTrials.gov, NCT04547907, and follow-up of the adjuvant phase is ongoing.
FINDINGS: Between Sept 20, 2020, and March 1, 2023, 789 patients were screened for eligibility, 689 of whom were randomly assigned (343 to the nab-paclitaxel group and 346 to the docetaxel plus carboplatin group). All 689 patients were Asian women. 669 patients received at least one dose of the study treatment and were included in the full analysis set (332 in the nab-paclitaxel group and 337 in the docetaxel plus carboplatin group). Median age of the patients was 50 years (IQR 43-55). Median follow-up time was 26 months (IQR 19-32). 220 (66.3% [95% CI 61.2-71.4]) patients in the nab-paclitaxel group had a pathological complete response, compared with 194 (57.6% [52.3-62.9]) in the docetaxel plus carboplatin group (combined odds ratio 1.54 [95% CI 1.10-2.14]; stratified p=0.011). 100 (30%) patients in the nab-paclitaxel group and 128 (38%) in the docetaxel plus carboplatin group had grade 3-4 adverse events. The most common grade 3-4 adverse events were nausea (22 [7%] in the nab-paclitaxel group vs 76 [23%] in the docetaxel plus carboplatin group), diarrhoea (25 [8%] vs 55 [16%]), and neuropathy (43 [13%] vs eight [2%]). Serious drug-related adverse events were reported in three (1%) patients in the nab-paclitaxel group and five (2%) in the docetaxel plus carboplatin group. No treatment-related deaths were reported in either group.
INTERPRETATION: These findings might suggest a potential advantage of nab-paclitaxel combined with trastuzumab and pertuzumab compared with the standard regimen in neoadjuvant therapy for patients with HER2-positive early breast cancer, suggesting that this new combination might establish a new standard for neoadjuvant treatment in this patient population.
FUNDING: National Natural Science Foundation of China, and Science and Technology Research Projects of Henan Province, China.
DOI: 10.1016/S1470-2045(24)00581-3
