血管内皮生长因子酪氨酸激酶抑制剂相关出血：一项网状荟萃分析。
Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis.
机构信息
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Pathology, University College of Medical Sciences, New Delhi, India.
出版信息
Crit Rev Oncol Hematol. 2021 Jan;157:103186. doi: 10.1016/j.critrevonc.2020.103186. Epub 2020 Dec 9.
BACKGROUND
Targeted therapies like vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are the first-choice treatment in several types of cancers. We aim to determine the comparative risk of bleeding events associated with the VEGFR-TKIs through a network meta-analysis.
METHODS
Published data search up to November 2018 reporting bleeding in cancer patients treated with VEGFR-TKIs was performed. The primary outcome was presence of hemorrhagic events at the end of the trial. Bleeding as a side-effect profile was examined for eleven VEGFR-TKIs (Apatinib, Brivanib, Cabozantinib, Lenvatinib, Motesanib, Nintedanib, Pazopanib, Regorafenib, Sorafenib, Sunitinib and Vandetanib). Network meta-analysis based on random effects model estimating Odds Ratio (OR) with 95 % confidence interval (CI), compared the risk of bleeding events among the VEGFR-TKIs with respect to placebo control conditions.
RESULTS
Fifty Randomized Clinical Trials (RCTs) including 16,753 cancer patients were included in this analysis. Twenty studies compared VEGFR-TKIs with placebo, the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. VEGFR-TKIs were associated with increased incidence of all-grade hemorrhagic events in comparison to control (standard chemotherapy and/or placebo) (OR = 1.79; 95 % CI 1.50-2.13, p-value <0.0001) and placebo (OR = 1.50; 95 % CI 1.16-1.93, p-value = 0.1). However, there was no difference in high-grade bleeding in patients treated with VEGFR-TKI in comparison to control (OR = 1.22; 95 % CI 0.87-1.71, p-value 0.74) or placebo alone (OR = 1.05; 95 % CI 0.65-1.70, p-value 0.73). Among individual VEGFR-TKIs, Sunitinib (OR = 3.31, 95 % CI 2.34-4.69) and Regorafenib (OR = 2.92, 95 % CI 1.50-5.71) were associated with higher risk of hemorrhagic events in comparison to placebo.
CONCLUSION
VEGR-TKIs, particularly Sunitinib and Regorafenib appear to be associated with increased risk of bleeding incidence.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42017056406.
背景
血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKIs）等靶向治疗是几种癌症的首选治疗方法。我们旨在通过网络荟萃分析确定与 VEGFR-TKIs 相关的出血事件的比较风险。
方法
对截至 2018 年 11 月报告接受 VEGFR-TKIs 治疗的癌症患者出血情况的已发表数据进行了搜索。主要结局是试验结束时出现出血事件。检查了 11 种 VEGFR-TKIs（阿帕替尼、贝伐单抗、卡博替尼、仑伐替尼、莫替沙尼、尼达尼布、帕唑帕尼、regorafenib、索拉非尼、舒尼替尼和凡德他尼）的出血作为副作用情况。基于随机效应模型的网络荟萃分析，用 95%置信区间（CI）估计比值比（OR），比较 VEGFR-TKIs 与安慰剂对照条件下出血事件的风险。
结果
本分析纳入了 50 项随机临床试验（RCT），包括 16753 名癌症患者。20 项研究比较了 VEGFR-TKIs 与安慰剂，其余研究比较了 VEGFR-TKIs 与标准化疗方案。与对照组（标准化疗和/或安慰剂）相比，VEGFR-TKIs 与所有级别出血事件的发生率增加相关（OR = 1.79；95%CI 1.50-2.13，p 值 <0.0001）和安慰剂（OR = 1.50；95%CI 1.16-1.93，p 值 = 0.1）。然而，与对照组相比，接受 VEGFR-TKI 治疗的患者的高级别出血无差异（OR = 1.22；95%CI 0.87-1.71，p 值 0.74）或单独安慰剂（OR = 1.05；95%CI 0.65-1.70，p 值 0.73）。在个别 VEGFR-TKIs 中，舒尼替尼（OR = 3.31，95%CI 2.34-4.69）和regorafenib（OR = 2.92，95%CI 1.50-5.71）与安慰剂相比，出血事件风险更高。
结论
VEGR-TKIs，特别是舒尼替尼和regorafenib，似乎与出血发生率增加有关。
试验注册号
PROSPERO CRD42017056406。
Zotero 插件