Incidence and risk of thromboembolism associated with bevacizumab in patients with non-small cell lung carcinoma
Incidence and risk of thromboembolism associated with bevacizumab in patients with non-small cell lung carcinoma
复制标题
非小细胞肺癌患者与贝伐珠单抗相关的血栓栓塞的发生率和风险
DOI：
10.21037/jtd.2018.07.09
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发表时间：
2018-08-01
影响因子：
2.5
通讯作者：
Zhong, Nan-Shan
中科院分区：
文献类型：
--
作者：
Li, Li-Juan;Chen, Di-Fei;Zhong, Nan-Shan
背景资料：贝伐单抗是一种抗血管内皮生长因子（VEGF）的重组人源化单克隆抗体，可有效治疗晚期非小细胞肺癌（NSCLC）。然而，在接受贝伐珠单抗治疗的NSCLC患者中报告了重度不良事件（AE）。目前，贝伐单抗对血栓栓塞症的作用仍有争议。我们进行了一项研究，以确定与贝伐单抗在NSCLC patient.Methods：电子数据库，如PubMed，Web of Science和科克伦图书馆的血栓栓塞的总体风险和发病率进行了搜索相关的试验。根据异质性，使用随机效应或固定效应模型进行统计分析，以计算总体发生率、比值比（OR）和95%置信区间（CI）。我们还使用了试验序列分析（TSA）来验证汇总结果。结果：共有来自9个研究的3,555名受试者。接受贝伐珠单抗治疗的NSCLC患者中血栓栓塞事件的总体发生率为4.8%（95% CI：1.9-7.7%）。在不使用贝伐珠单抗的情况下，该发生率为2.9%（95% CI：0.6-5.1%）。贝伐珠单抗的使用与血栓栓塞事件的风险显著增加相关（OR =1.74; 95% CI：1.15-2.62; P=0.008）。基于剂量的亚组分析显示，15 mg/kg剂量的贝伐珠单抗（OR =1.81; 95% CI：1.14-2.86; P=0.012），但不是7.5 mg/kg（OR =1.32; 95%CI：0.78-2.24; P=0.296），增加血栓栓塞的风险。贝伐珠单抗与NSCLC患者血栓栓塞发生风险显著增加相关。可能存在剂量-毒性关系，小剂量贝伐珠单抗可能是NSCLC患者更好的选择，疗效相当，血栓栓塞事件风险低。
Background: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective for the treatment of advanced non-small cell lung cancer (NSCLC). However, severe adverse events (AEs) have been reported in NSCLC patients treated with bevacizumab. Currently, the contribution of Bevacizumab to thromiboemibolism is still controversial. We conducted a study to determine the overall risk and incidence of thromboembolism with bevacizumab in NSCLC patients.Methods: Electronic databases such as the PubMed, Web of Science and Cochrane Library were searched for related trials. Statistical analyses were conducted to calculate the overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) by using either random-effect or fixed-effect models depending on the heterogeneity. We also used trial sequence analysis (TSA) to verify the pooled result.Results: A total of 3,555 subjects from nine studies were included. The overall incidence of thromboembolism events in NSCLC patients treated with bevacizumab was 4.8% (95% CI: 1.9-7.7%). Without bevacizumab, this incidence was 2.9% (95% CI: 0.6-5.1%). Bevacizumab use was associated with a significantly increased risk in thromboembolism events (OR =1.74; 95% CI: 1.15-2.62; P=0.008). Subgroup analysis based on the doses showed that bevacizumab administered at 15 mg/kg (OR =1.81; 95% CI: 1.14-2.86; P=0.012), but not 7.5 mg/kg (OR =1.32; 95% CI: 0.78-2.24; P=0.296), increased the risk of thromboembolism.Conclusions: Bevacizumab is associated with a significantly increased risk of thromboembolism development in NSCLC patients. It may have dose-toxicity relationship and low dose of bevacizumab may be a better choice for NSCLC patients, with equal efficacy and low hazard of thromboembolism events.