近日，新乡医学院第一附属医院康小红团队研究了EGFR突变的非小细胞肺癌中与表皮生长因子受体酪氨酸激酶抑制剂相关的心血管不良事件。该研究于2025年9月2日发表在《英国医学杂志》上。

为了评估EGFR突变的非小细胞肺癌（NSCLC）患者与表皮生长因子受体（EGFR）酪氨酸激酶抑制剂相关的心血管不良事件的风险，研究组在PubMed， Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials，以及三个临床试验注册中心中检索从成立到2024年11月20日的相关文献，筛选出比较EGFR酪氨酸激酶抑制剂单药治疗与安慰剂或其他治疗在EGFR突变的NSCLC患者中的疗效的随机对照试验，进行了一项系统评价和网络荟萃分析。

对审稿人进行数据提取和偏倚风险评估。随机效应网络荟萃分析使用频率分析方法比较了不同治疗方法的药物不良反应。使用网络置信度荟萃分析方法评估证据的确定性。两两荟萃分析比较了三代EGFR酪氨酸激酶抑制剂。

网络荟萃分析包括89项随机对照试验，涉及29813名参与者，平均随访2.18年。与安慰剂相比，第一代（优势比1.51，95%可信区间1.01 - 2.26；高确定性；合并发病率3.2%）和第三代EGFR酪氨酸激酶抑制剂（优势比2.18,1.46 - 3.27；高确定性；9.5%）均与心脏不良事件风险增加相关。在第三代抑制剂中，奥西替尼（2.53,1.53 - 4.19，高确定性，8.9%）和拉泽替尼（2.84,1.17 - 6.91，中等确定性，2.7%）与心脏不良事件相关。

联合治疗，如抗血管生成与厄洛替尼或吉非替尼，与血管不良事件相关（高确定性），而抗血管生成与奥希替尼与心血管不良事件相关（中等至高确定性）。此外，使用第三代抑制剂(如单独使用奥西替尼（3.35,1.75至6.40，高确定性，6.2%）和联合使用抗血管生成药物时，心律失常的风险明显更高（3.26,1.83至5.81，高确定性，7.3%）。Almonertinib与血管毒性有关。在两两荟萃分析中，与第一代抑制剂相比，第三代抑制剂与任何级别和≥3级心血管不良事件的风险相关。

研究结果表明，在EGFR突变的NSCLC患者中，第一代和第三代EGFR酪氨酸激酶抑制剂以及联合抗血管生成治疗与心血管不良事件的风险增加相关。与第一代抑制剂相比，第三代抑制剂的风险明显更高。

附：英文原文

Title: Cardiovascular adverse events associated with epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer: systematic review and network meta-analysis

Author: Zidong Ma, Fei Cao, Mingjuan Liao, Rui Min, Rui Zheng, Xiaolin Sun, Xinlin Chen, Yabin Gong, Sizhi Ai, Xiaohong Kang

Issue&Volume: 2025/09/02

Abstract:

Objective To evaluate the risk of cardiovascular adverse events associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer (NSCLC).

Design Systematic review and network meta-analysis.

Data sources PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and three clinical trial registries, from inception to 20 November 2024.

Study selection Randomised controlled trials comparing EGFR tyrosine kinase inhibitor monotherapy with placebo or other treatments in patients with EGFR-mutated NSCLC.

Data extraction and synthesis Pairs of reviewers extracted data and assessed risk of bias. A random effects network meta-analysis using a frequentist approach compared adverse drug reactions across different treatments. Certainty of evidence was evaluated using the confidence in network meta-analysis approach. Pairwise meta-analyses were done to compare the three generations of EGFR tyrosine kinase inhibitors.

Results The network meta-analysis comprised 89 randomised controlled trials involving 29813 participants, mean follow-up 2.18 years. Compared with placebo, both first generation (odds ratio 1.51, 95% confidence interval 1.01 to 2.26; high certainty; pooled incidence 3.2%) and third generation EGFR tyrosine kinase inhibitors (2.18, 1.46 to 3.27; high certainty; 9.5%) were associated with increased risks of cardiac adverse events. Among third generation inhibitors, osimertinib (2.53, 1.53 to 4.19; high certainty; 8.9%) and lazertinib (2.84, 1.17 to 6.91; moderate certainty; 2.7%) were associated with cardiac adverse events. Combined therapies, such as antiangiogenesis with erlotinib or gefitinib, were associated with vascular adverse events (high certainty), whereas antiangiogenesis with osimertinib was associated with cardiovascular adverse events (moderate to high certainty). Also, the risk of arrhythmias was significantly higher with third generation inhibitors (3.26, 1.83 to 5.81; high certainty; 7.3%), such as osimertinib alone (3.35, 1.75 to 6.40; high certainty; 6.2%) and in combination with antiangiogenesis. Almonertinib was associated with vascular toxicity. In pairwise meta-analysis, third generation inhibitors were associated with higher risks of any grade and grade ≥3 cardiovascular adverse events compared with first generation inhibitors.

Conclusions In patients with EGFR-mutated NSCLC, first and third generation EGFR tyrosine kinase inhibitors, as well as combination therapies with antiangiogenesis, were associated with increased risks of cardiovascular adverse events. Risks were significantly higher with third generation compared with first generation inhibitors.

DOI: 10.1136/bmj-2024-082834

Source: https://www.bmj.com/content/390/bmj-2024-082834