曲妥珠单抗鞘内与其他给药途径用于 HER2 阳性乳腺癌脑膜转移患者的 HER2 靶向治疗的比较。

Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases.

机构信息

Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.

Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada; Faculty of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

Breast. 2023 Jun;69:451-468. doi: 10.1016/j.breast.2023.04.008. Epub 2023 May 1.

DOI:10.1016/j.breast.2023.04.008

PMID:37156650

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10300571/

Abstract

BACKGROUND

Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.

METHODS

We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.

RESULTS

7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.

CONCLUSIONS

The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.

摘要

背景

HER2+ 乳腺癌（BC）患者常发生脑膜转移（LM）。虽然 HER2 靶向治疗在新辅助、辅助和转移性环境中已显示出疗效，包括实质脑转移，但其在 HER2+BCLM 患者中的疗效尚未在随机对照试验中进行研究。然而，一些单臂前瞻性研究、病例系列和病例报告已经研究了口服、静脉或鞘内给予 HER2 靶向治疗方案治疗 HER2+BCLM 患者。

方法

我们按照 PRISMA 指南对个体患者数据进行了系统评价和荟萃分析，以评估 HER2 靶向治疗在 HER2+BCLM 中的疗效。评估的靶向治疗药物包括曲妥珠单抗（鞘内或静脉内）、帕妥珠单抗、拉帕替尼、奈拉替尼、图卡替尼、曲妥珠单抗-美坦新和曲妥珠单抗-德曲妥珠单抗。主要终点是总生存期（OS），次要终点是中枢神经系统特异性无进展生存期（CNS-PFS）。

结果

筛选了 7780 篇摘要，确定了 45 篇文献，共纳入了 208 例患者，对应了 275 例 HER2 靶向治疗 BCLM 的治疗线，符合纳入标准。在单变量和多变量分析中，我们观察到鞘内曲妥珠单抗与口服或静脉内 HER2 靶向治疗相比，OS 和 CNS-PFS 无显著差异。抗 HER2 单克隆抗体方案并不优于 HER2 酪氨酸激酶抑制剂。在 15 例患者的队列中，与其他 HER2 靶向治疗药物相比，与曲妥珠单抗-德曲妥珠单抗治疗相比，OS 延长。