背景:脑转移(BMs)是HER2阳性转移性乳腺癌(MBC)患者的常见事件,并与不良预后相关。小分子抗HER2酪氨酸激酶抑制剂(TKIs)是治疗BM的有前景的药物。在这项研究中,我们评估了接受含TKI方案治疗的HER2阳性MBC和BM患者与接受不含TKI方案治疗的患者的临床结局.
方法:PubMed,Embase,科克伦图书馆,和会议记录(ASCO,SABCS,ESMO,和ESMO乳腺)被搜索到2021年6月。主要终点是BM患者的无进展生存期(PFS)。次要终点包括无BM患者的PFS和总生存期(OS)。该研究是根据系统评价和荟萃分析(PRISMA)指南的首选报告项目进行的。使用随机效应模型汇集总体效应。
结果:本系统综述和荟萃分析包括来自五项评估tucatinib-,lapatinib-,pyrotinib-,或基于阿法替尼的组合。在有BM[风险比(HR)0.67,95%置信区间(CI)0.41-1.12;P=0.13]和无BM(HR0.55,95%CI0.24-1.26;P=0.16)的患者中,观察到有利于含TKI方案的无统计学意义的PFS益处。敏感性分析,单独排除每一项研究,在分析中排除阿法替尼后,BM患者的PFS获益显著(HR0.56,95%CI0.35-0.90;P=0.016).对照组之间的OS没有观察到统计学上的显着差异。
结论:在BM患者中观察到PFS倾向于包含TKI的治疗方案。敏感性分析,仅包括评估含有tucatinib的方案的试验,拉帕替尼,或pyrotinib在BM患者中显示出显着的PFS益处,有利于含TKI的方案。
BACKGROUND: Brain metastases (BMs) are frequent events in patients with HER2-positive metastatic breast cancer (MBC) and are associated with poor prognosis. Small-molecule anti-HER2 tyrosine kinase inhibitors (TKIs) are promising agents for the treatment of BM. In this study, we assess the clinical outcomes of patients with HER2-positive MBC and BM treated with TKI-containing regimens compared with those treated with non-TKI-containing regimens.
METHODS: PubMed, Embase, Cochrane Library, and conference proceedings (ASCO, SABCS, ESMO, and ESMO Breast) were searched up to June 2021. The primary endpoint was progression-free survival (PFS) in patients with BM. Secondary endpoints included PFS in patients without BM and overall survival (OS). The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall effects were pooled using random-effects models.
RESULTS: This systematic
review and meta-analysis included data from 2437 patients (490 with and 1947 without BM at baseline) enrolled in five trials assessing tucatinib-, lapatinib-, pyrotinib-, or
afatinib-based combinations. A nonstatistically significant PFS benefit favoring TKI-containing regimens was observed in both patients with BM [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.41-1.12; P = 0.13] and without BM (HR 0.55, 95% CI 0.24-1.26; P = 0.16). Sensitivity analysis, excluding each study singly, demonstrated a significant PFS benefit favoring TKI-containing regimens in patients with BM after the exclusion of
afatinib from the analysis (HR 0.56, 95% CI 0.35-0.90; P = 0.016). No statistically significant differences in OS were observed between the comparison groups.
CONCLUSIONS: A trend in PFS favoring TKI-containing regimens was observed in patients with BM. Sensitivity analysis including only trials that evaluated regimens containing tucatinib, lapatinib, or pyrotinib demonstrated a significant PFS benefit favoring TKI-containing regimens in patients with BM.