Erickson Anders Wilder, Habbous Steven, Hoey Christianne, Jerzak Katarzyna J, Das Sunit
Institute of Medical Science, University of Toronto, Toronto, Canada.
Ontario Health (Cancer Care Ontario), Toronto, ON, Canada.
NPJ Breast Cancer. 2021 Feb 18;7(1):17. doi: 10.1038/s41523-021-00220-0.
Observational studies have suggested that HER2 inhibition with trastuzumab may be associated with an increased incidence of intracranial metastatic disease (IMD) due to its ability to prolong survival. We hypothesized that prolonged survival associated with dual-agent HER2 inhibition may be associated with an even higher incidence of IMD. This study pooled estimates of IMD incidence and survival among patients with HER2-positive breast cancer receiving dual- versus single-agent HER2 targeted therapy, as well as trastuzumab versus chemotherapy, observation, or another HER2-targeted agent. We searched PubMed, EMBASE, and CENTRAL from inception to 25 March 2020. We included randomized controlled trials that reported IMD incidence for patients with HER2-positive breast cancer receiving trastuzumab as the experimental or control arm irrespective of disease stage. Among 465 records identified, 19 randomized controlled trials (32,572 patients) were included. Meta-analysis of four studies showed that dual HER2-targeted therapy was associated with improved overall survival (HR 0.76; 95% CI, 0.66-0.87) and progression-free survival (HR 0.77; 95% CI, 0.68-0.87) compared to single HER2-targeted therapy, but the risk of IMD was similar (RR 1.03; 95% CI, 0.83-1.27). Our study challenges the hypothesis that prolonged survival afforded by improved extracranial disease control is associated with increased IMD incidence.
观察性研究表明，曲妥珠单抗抑制HER2可能会因延长生存期而导致颅内转移性疾病（IMD）的发病率增加。我们推测，与双联HER2抑制相关的生存期延长可能与更高的IMD发病率相关。本研究汇总了接受双联与单联HER2靶向治疗、曲妥珠单抗与化疗、观察或其他HER2靶向药物治疗的HER2阳性乳腺癌患者的IMD发病率和生存期估计值。我们检索了从数据库建立至2020年3月25日的PubMed、EMBASE和CENTRAL。我们纳入了随机对照试验，这些试验报告了接受曲妥珠单抗作为试验组或对照组的HER2阳性乳腺癌患者的IMD发病率，无论疾病分期如何。在识别出的465条记录中，纳入了19项随机对照试验（32572例患者）。四项研究的荟萃分析表明，与单联HER2靶向治疗相比，双联HER2靶向治疗可改善总生存期（HR 0.76；95%CI，0.66 - 0.87）和无进展生存期（HR 0.77；95%CI，0.68 - 0.87），但IMD风险相似（RR 1.03；95%CI，0.83 - 1.27）。我们的研究对以下假设提出了质疑，即颅外疾病控制改善所带来的生存期延长与IMD发病率增加相关。
