血管内皮生长因子通路小分子酪氨酸激酶抑制剂所致血压升高与实体肿瘤患者远期预后相关性的荟萃分析

Correlation between drug-induced blood pressure elevation and long-term prognosis of tumor patients treated with small molecule tyrosine kinase inhibitors targeted to the vascular endothelial growth factor pathway: a meta-analysis

  • 摘要: 目的 评估血管内皮生长因子(VEGF)通路小分子酪氨酸激酶抑制剂(TKI)治疗实体肿瘤过程中所致的血压升高与抗肿瘤疗效及远期预后的关联。方法 遵循Cochrane 协作方法及《系统综述和荟萃分析优先报告的条目》(PRISMA)和《推荐意见分级评估、制定和评价》(GRADE)指南,检索并纳入评估VEGF通路TKI治疗实体肿瘤过程中血压升高与患者预后之间的相关性且评估指标为客观反应率(ORR)、无进展生存期(PFS)及总生存期(OS)的观察性研究、回顾性研究或前瞻性随机对照试验,进行数据提取,并对所有研究按照纽卡斯尔-渥太华量表(NOS)进行质量评价。主要终点为OS,次要终点为PFS与ORR。结果 最终纳入研究58项,共10 020例患者,TKI所致血压升高与患者OS与血压未升高相比,血压升高者发生死亡事件的风险比(HR)为0.54(95%CI 0.49~0.61,P<0.001)、PFS血压升高者发生疾病进展事件的HR为0.55(95%CI 0.48~0.63,P<0.001)、ORR(RR=1.86,95%CI 1.43~2.41,P<0.001)均具有相关性。以干预药物及肿瘤类型分组进行亚组分析,仍存在类似结果。结论 VEGF通路TKI类药物治疗实体肿瘤中药物相关性血压升高提示患者预后更佳,即血压升高可能为治疗有效的生物学标志,但由于本文纳入文献具有较大异质性,因此对该结论应谨慎解读。

     

    Abstract: Objective To evaluate whether blood pressure elevation induced by small molecule tyrosine kinase inhibitors (TKI) targeted to the vascular endothelial growth factor (VEGF) pathway in the treatment of solid tumors is correlated with the anti-tumor efficacy and long-term prognosis. Methods A systematic review with a meta-analysis was conducted using Cochrane Collaboration methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Observational, retrospective or prospective randomized controlled studies were included if they evaluated the correlation between TKI-induced blood pressure elevation and prognosis of patients, with at least one of the following indicators: objective response rate (ORR), progression-free survival (PFS) or overall survival (OS). Data were extracted and all studies were assessed for quality according to the Newcastle-Ottawa Scale (NOS). The primary outcome of this study was OS, while the secondary outcomes were PFS and ORR. Results A total of 58 studies were considered eligible, with 10 020 patients included. TKI-induced blood pressure elevation was significantly correlated with OS HR was 0.54 (95%CI 0.49-0.61, P<0.001) for death in patients with elevated blood pressure compared with those without, and PFS HR was 0.55 (95%CI 0.48-0.63, P<0.001) for disease progression in patients with elevated blood pressure compared with those without, as well as better ORR (RR=1.86, 95%CI 1.43-2.41, P<0.001). The subgroup analyses by intervention drugs and tumor types had similar results. Conclusion TKI-induced blood pressure elevation is significantly correlated with better prognosis of tumor patients, thereby it may be one of the biological markers of TKI treatment. However, due to the considerable heterogeneity among the included studies in this article, caution should be exercised in interpreting this conclusion.

     

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