Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Pathology, University College of Medical Sciences, New Delhi, India.
Crit Rev Oncol Hematol. 2021 Jan;157:103186. doi: 10.1016/j.critrevonc.2020.103186. Epub 2020 Dec 9.
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.
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.
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.
VEGR-TKIs, particularly Sunitinib and Regorafenib appear to be associated with increased risk of bleeding incidence.
PROSPERO CRD42017056406.
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。
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。
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。
VEGR-TKIs，特别是舒尼替尼和regorafenib，似乎与出血发生率增加有关。
PROSPERO CRD42017056406。
