TCHL——一项II期新辅助研究，评估TCH（多西他赛、卡铂和曲妥珠单抗）和TCHL（多西他赛、卡铂、曲妥珠单抗和拉帕替尼）用于HER-2阳性乳腺癌患者：一项进行血清生物标志物分析的5年随访研究。
TCHL - a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, trastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis.
作者信息
Crown John, Eustace Alex J, Collins Denis M, Keane Maccon, Coate Linda, Kennedy John, O'Reilly Seamus, Kelly Catherine, O'Connor Miriam, Martin Michael, Murphy Conleth, Duffy Karen, Walshe Janice, Gullo Giuseppe, Mahgoub Thamir, Alvarez-Iglesias Alberto, Parker Imelda, Donachie Vicky, Teiserskiene Ausra, Madden Stephen F, Moulton Brian, O'Donovan Norma, Hennessy Bryan T
机构信息
Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland; Life Sciences Institute, Dublin City University, Dublin, Ireland.
Life Sciences Institute, Dublin City University, Dublin, Ireland; School of Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland.
出版信息
Acta Oncol. 2025 Jun 5;64:751-760. doi: 10.2340/1651-226X.2025.43143.
BACKGROUND
The docetaxel (T), carboplatin (C) and trastuzumab (H) regimen has been used in the (neo-) adjuvant treatment of HER2+ early stage breast cancer (ESBC). Lapatinib (L) a small molecule HER2 antagonist produces clinical responses following H failure.
METHODS
We randomly assigned 88 patients with stages Ic-III HER2+ESBC to receive neoadjuvant TCH, TCL or TCHL followed by surgery and 1 year of H. The primary endpoint was pathological complete response (pCR). Secondary objectives were overall and disease-free survival (OS, DFS).
RESULTS
The TCL arm was closed following demonstration of inferiority of L in another trial. The pCR rates for TCH and TCHL were 52.8 and 51.6 (p = 1.0). At a median 4.8 years follow-up, TCHL patients had a significantly superior DFS; however, OS was similar. Prophylactic loperamide reduced the frequency of diarrhoea. Serum biomarker analysis identified a link between high tumour T-cell levels and high red blood cell, haematocrit, and haemoglobin following commencement of therapy.
INTERPRETATION
The study did not meet its primary endpoint of superior pCR. TCHL produced a significant improvement in DFS. Our study and others suggest a possible role for L in neoadjuvant therapy of HER2+ ESBC.
CLINICAL TRIAL REGISTRATION
NCT01485926.
背景
多西他赛（T）、卡铂（C）和曲妥珠单抗（H）方案已用于HER2阳性早期乳腺癌（ESBC）的（新）辅助治疗。拉帕替尼（L）是一种小分子HER2拮抗剂，在H治疗失败后可产生临床反应。
方法
我们将88例Ic-III期HER2阳性ESBC患者随机分配接受新辅助TCH、TCL或TCHL治疗，随后进行手术及1年的H治疗。主要终点是病理完全缓解（pCR）。次要目标是总生存期和无病生存期（OS、DFS）。
结果
在另一项试验证明L疗效较差后，TCL组研究终止。TCH组和TCHL组的pCR率分别为52.8%和51.6%（p = 1.0）。在中位随访4.8年时，TCHL组患者的DFS显著更优；然而，OS相似。预防性使用洛哌丁胺可降低腹泻频率。血清生物标志物分析确定了治疗开始后高肿瘤T细胞水平与高红细胞、血细胞比容和血红蛋白之间的联系。
解读
该研究未达到其主要终点，即pCR更优。TCHL方案使DFS有显著改善。我们的研究及其他研究表明L在HER2阳性ESBC新辅助治疗中可能发挥作用。
临床试验注册号
NCT01485926。
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