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.

Methods

Systematic reviewand network meta-analysis.

系统评价和网络荟萃分析。

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.

从建库至2024年11月20日，检索了PubMed、Embase、Web of Science、Scopus、Cochrane中央对照试验注册处以及三个临床试验注册处的资料。

study_selection

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

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突变型非小细胞肺癌患者中的随机对照试验。

data_extraction_and_synthesis

Pairs of reviewers extracted data and assessed risk of bias.

成对的审查员提取数据并评估偏倚风险。

A random effects network meta-analysisusing a frequentist approach compared adverse drug reactions across different treatments.

使用频率主义方法的随机效应网络荟萃分析比较了不同治疗方案之间的不良药物反应。

Certainty of evidence was evaluated using the confidence in network meta-analysisapproach.

使用网络荟萃分析方法评估了证据的确定性。

Pairwise meta-analyses were done to compare the three generations of EGFR tyrosine kinase inhibitors.

进行了成对荟萃分析，以比较三代EGFR酪氨酸激酶抑制剂。

Results

The network meta-analysiscomprised 89 randomised controlled trials involving 29 813 participants, mean follow-up 2.18 years.

这项网络荟萃分析包括了89项随机对照试验，涉及29,813名参与者，平均随访时间为2.18年。

Compared with placebo, both first generation (odds ratio 1.51, 95% confidence interval1.01 to 2.26; high certainty; pooled incidence3.2%) 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.

与安慰剂相比，第一代（比值比1.51，95%置信区间1.01至2.26；高确定性；汇总发生率3.2%）和第三代EGFR酪氨酸激酶抑制剂（2.18，1.46至3.27；高确定性；9.5%）均与心脏不良事件风险增加相关。

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.

在第三代抑制剂中，奥希替尼（2.53，95% 置信区间1.53至4.19；高确定性；8.9%）和拉泽替尼（2.84，95% 置信区间1.17至6.91；中等确定性；2.7%）与心脏不良事件相关。

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).

联合疗法，如与厄洛替尼或吉非替尼联合的抗血管生成治疗，与血管不良事件相关（高确定性），而与奥希替尼联合的抗血管生成治疗则与心血管不良事件相关（中等到高确定性）。

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.

此外，使用第三代抑制剂（例如单独使用奥希替尼或与抗血管生成药物联合使用）时，心律失常的风险显著更高（3.26，1.83至5.81；高确定性；7.3%），如单独使用奥希替尼（3.35，1.75至6.40；高确定性；6.2%）和与抗血管生成药物联合使用时。

Almonertinib was associated with vascular toxicity.

Almonertinib与血管毒性相关。

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.

在成对的荟萃分析中，第三代抑制剂与第一代抑制剂相比，与任何级别的心血管不良事件和3级或更高级别的心血管不良事件的较高风险相关。

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.

在EGFR突变型非小细胞肺癌患者中，第一代和第三代EGFR酪氨酸激酶抑制剂以及与抗血管生成药物的联合治疗，与心血管不良事件风险增加相关。

Risks were significantly higher with third generation compared with first generation inhibitors.

与第一代抑制剂相比，第三代抑制剂的风险显著更高。

systematic_review_registration

PROSPERO CRD42023433003.

PROSPERO CRD42023433003。