单靶、双靶治疗与乳腺癌脑转移风险

　　若干观察研究结果表明，曲妥珠单抗对HER2的抑制作用，与颅内转移发生比例显著相关，据推测或许由于曲妥珠单抗能够延长生存时间。

　　2021年2月18日，英国《自然》旗下《乳腺癌》在线发表加拿大多伦多大学、安大略癌症中心、森尼布鲁克健康科学中心的系统回顾和荟萃分析，比较了双药与单药HER2抑制剂对乳腺癌患者生存率和颅内转移发生率的影响。

　　作者通过PubMed、EMBASE、CENTRAL对2020年3月25日前发表的HER2阳性乳腺癌患者曲妥珠单抗单药或双药抗HER2靶向治疗随机对照研究进行文献检索，对患者生存率和颅内转移发生率进行汇总分析。

　　结果，从465篇文献筛选出19项随机对照研究（3万2572例患者）包括患者生存率和颅内转移发生率数据。

　　其中4项研究（NeoALTTO、ALTTO、APHINITY、CLEOPATRA）对曲妥珠单抗单药或双药抗HER2靶向治疗进行了比较，荟萃分析表明，双药与单药相比：

  • 全因死亡风险低24%（风险比：0.76，95%置信区间：0.66～0.87）

  • 进展死亡风险低23%（风险比：0.77，95%置信区间：0.68～0.87）

  • 颅内转移风险相似（相对风险：1.03，95%置信区间：0.83～1.27）

　　因此，该研究结果表明，对于HER2阳性乳腺癌患者，双药与单药相比，可减少死亡风险、延长生存时间，并未增加颅内转移风险。

NPJ Breast Cancer. 2021 Feb 18. Online ahead of print.

Dual- versus single-agent HER2 inhibition and incidence of intracranial metastatic disease: a systematic review and meta-analysis.

Anders Wilder Erickson, Steven Habbous, Christianne Hoey, Katarzyna J. Jerzak, Sunit Das.

University of Toronto, Toronto, Canada; Ontario Health (Cancer Care Ontario), Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, Canada.

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.

DOI: 10.1038/s41523-021-00220-0

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