Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK; The Clatterbridge Cancer Centre NHS Foundation Trust, 65 Pembroke Place, Liverpool, L7 8YA, United Kingdom.
Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XR, UK.
Breast. 2022 Jun;63:85-100. doi: 10.1016/j.breast.2022.03.013. Epub 2022 Mar 22.
The introduction of human epidermal growth factor receptor 2 (HER2) directed therapy has transformed the outcomes of patients with advanced breast cancer (BC). However, HER2 positive breast cancer has a predilection for the central nervous system (CNS) which is associated with significant morbidity and mortality. Understanding the intracranial activity of novel HER2 directed agents is key to developing treatments as well as possible preventative strategies for HER2-positive CNS disease.
Using protocols and data from published phase III clinical trials for locally advanced/metastatic HER2-positive breast cancer since the licensing of single agent trastuzumab for advanced BC we review the central nervous system related aspects. This includes CNS related entry criteria, use of baseline and on study cross-sectional imaging of the CNS and protocol and non-protocol defined CNS end points and reported data.
and Relevance: This review found heterogeneity between studies with regard to the entry criteria, use of CNS imaging and reported end points within the pivotal phase III studies. Based on these data, a standardisation of both entry criteria and end points with regard to the CNS should be developed and applied to future studies of HER2-positive advanced BC. Such an approach would enable the generation of comparable data and allow a meaningful analysis of different treatment approaches with regard to the CNS. This in turn would allow the development of the most optimal treatment approaches for HER2 positive CNS disease and ultimately the development of preventative strategies.
人表皮生长因子受体 2（HER2）靶向治疗的引入改变了晚期乳腺癌（BC）患者的预后。然而，HER2 阳性乳腺癌易发生中枢神经系统（CNS）转移，这与较高的发病率和死亡率相关。了解新型 HER2 靶向药物的颅内活性对于开发治疗方法以及针对 HER2 阳性 CNS 疾病的可能预防策略至关重要。
自单药曲妥珠单抗获批用于晚期 BC 以来，我们使用已发表的局部晚期/转移性 HER2 阳性乳腺癌 III 期临床试验方案和数据，综述了与 CNS 相关的方面。这包括 CNS 相关入组标准、基线和研究期间 CNS 横断面成像的使用、方案和非方案定义的 CNS 终点以及报告的数据。
本综述发现，关键性 III 期研究在入组标准、CNS 影像学的使用和报告的终点方面存在异质性。基于这些数据，应制定和应用针对 CNS 的入组标准和终点的标准化，以应用于未来的 HER2 阳性晚期 BC 研究。这种方法将能够生成可比的数据，并对 CNS 方面的不同治疗方法进行有意义的分析。这反过来又将允许开发针对 HER2 阳性 CNS 疾病的最佳治疗方法，并最终开发预防策略。
