Huo Xingfa, Shen Guoshuang, Wang Tianzhuo, Li Jinming, Xie Qiqi, Liu Zhen, Wang Miaozhou, Zhao Fuxing, Ren Dengfeng, Zhao Jiuda
Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China.
Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Front Oncol. 2023 Feb 20;13:1003565. doi: 10.3389/fonc.2023.1003565. eCollection 2023.
Many systemic treatment options are available for patients with human epidermal growth factor 2 (HER2)-positive breast cancer brain metastases. However, it is unclear which pharmacological treatment option is the most beneficial.
We searched databases, such as PubMed, Embase, and Cochrane Library, and conference abstracts according to keywords. We extracted progression-free survival (PFS), overall survival (OS) data, and overall response rate (ORR) from randomized controlled trials and single-arm studies of HER2-positive breast cancer brain metastasis treatment for meta-analysis and analyzed different drug-related adverse events (AEs).
Three randomized controlled trials and seven single-arm clinical studies with 731 patients with HER2-positive brain metastases from breast cancer involving at least seven drugs were included. In randomized controlled trials, our results showed that trastuzumab deruxtecan significantly improved PFS and OS in patients and was superior to other drug regimens. In the single-arm study, the ORR was more pronounced for the trastuzumab deruxtecan and pyrotinib plus capecitabine regimens (ORR, 73.33%; 95% confidence intervals [CI], 44.90%-92.21%; ORR, 74.58%; 95% CI, 61.56%-85.02%, respectively). We found that the main AEs of antibody-drug conjugate (ADC) were nausea and fatigue, while the main AE of small-molecule tyrosine kinase inhibitor (TKI) drugs and large monoclonal antibodies was diarrhea.
Trastuzumab deruxtecan was shown to be the most significant in improving survival in patients with HER2-positive breast cancer brain metastases in network meta-analysis, and in single-arm study, patients with HER2-positive breast cancer brain metastases treated with trastuzumab deruxtecan and pyrotinib plus capecitabine regimen had the highest ORR. The main AEs associated with ADC, large monoclonal antibodies, and TKI drugs were nausea, fatigue, and diarrhea, respectively.
对于人表皮生长因子2（HER2）阳性乳腺癌脑转移患者，有多种全身治疗方案可供选择。然而，尚不清楚哪种药物治疗方案最为有益。
我们根据关键词检索了PubMed、Embase和Cochrane图书馆等数据库以及会议摘要。我们从HER2阳性乳腺癌脑转移治疗的随机对照试验和单臂研究中提取无进展生存期（PFS）、总生存期（OS）数据和总缓解率（ORR）进行荟萃分析，并分析不同的药物相关不良事件（AE）。
纳入了三项随机对照试验和七项单臂临床研究，共731例HER2阳性乳腺癌脑转移患者，涉及至少七种药物。在随机对照试验中，我们的结果显示，曲妥珠单抗德瓦鲁单抗显著改善了患者的PFS和OS，且优于其他药物方案。在单臂研究中，曲妥珠单抗德瓦鲁单抗和吡咯替尼联合卡培他滨方案的ORR更为显著（ORR分别为73.33%；95%置信区间[CI]，44.90%-92.21%；ORR为74.58%；95%CI，61.56%-85.02%）。我们发现，抗体药物偶联物（ADC）的主要AE是恶心和疲劳，而小分子酪氨酸激酶抑制剂（TKI）药物和大型单克隆抗体的主要AE是腹泻。
在网络荟萃分析中，曲妥珠单抗德瓦鲁单抗在改善HER2阳性乳腺癌脑转移患者生存率方面最为显著，并且在单臂研究中，接受曲妥珠单抗德瓦鲁单抗和吡咯替尼联合卡培他滨方案治疗的HER2阳性乳腺癌脑转移患者的ORR最高。与ADC、大型单克隆抗体和TKI药物相关的主要AE分别是恶心、疲劳和腹泻。
