Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
Faculty of Health Sciences, McMaster University, Hamilton, Canada.
Lung Cancer. 2021 Nov;161:9-17. doi: 10.1016/j.lungcan.2021.08.014. Epub 2021 Aug 31.
Anaplastic Lymphoma Kinase (ALK) inhibitors have revolutionized the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC), improving progression-free survival. Bradycardia is a potential adverse effect of these agents. We aimed to determine the risk of bradycardia associated with ALK inhibitors in patients with advanced NSCLC.
We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, National clinical trial registry, and Web of Science Core Collection. We included all randomized controlled trials in which an ALK-inhibitor was compared with another ALK-inhibitor or standard chemotherapy. Meta-analyses were conducted to evaluate the pooled incidence rates of bradycardia and dizziness using fixed effect models.
The pooled incidence of bradycardia among 1737 individuals prescribed ALK inhibitors was 8% during a mean follow-up of 1.26 years. Crizotinib led to more bradycardia than standard chemotherapy (relative risk, RR 24.68, 95% CI 7.11-85.), while no difference was seen between crizotinib and alectinib (RR 1.12, 95% CI 0.79-1.59). The next-generation ALK inhibitors alectinib, brigatinib and lorlatinib combined resulted in a similar rate of bradycardia when compared to crizotinib (RR 0.77, 95% CI 0.57-1.04). All ALK inhibitors (as an aggregate) caused more dizziness (as a potential symptom of bradycardia) than standard chemotherapy (RR 1.88, 95% CI 1.44-2.44).
Crizotinib for the treatment of NSCLC is associated with a higher risk for bradycardia compared to standard chemotherapy. There is no evidence of a difference in bradycardia risk between crizotinib and newer ALK inhibitors.
间变性淋巴瘤激酶（ALK）抑制剂改变了晚期 ALK 阳性非小细胞肺癌（NSCLC）的治疗方法，改善了无进展生存期。心动过缓是这些药物的潜在不良反应。我们旨在确定ALK 抑制剂治疗晚期 NSCLC 患者时与心动过缓相关的风险。
我们对 MEDLINE、EMBASE、Cochrane 对照试验中心注册库、国家临床试验注册库和 Web of Science 核心合集进行了系统搜索。我们纳入了所有将 ALK 抑制剂与另一种 ALK 抑制剂或标准化疗进行比较的随机对照试验。使用固定效应模型进行荟萃分析，以评估心动过缓和头晕的 pooled 发生率。
在平均随访 1.26 年期间，1737 名接受 ALK 抑制剂治疗的个体中，心动过缓的 pooled 发生率为 8%。克唑替尼导致的心动过缓发生率高于标准化疗（相对风险，RR 24.68，95%CI 7.11-85.），而克唑替尼与阿来替尼（RR 1.12，95%CI 0.79-1.59）之间无差异。下一代 ALK 抑制剂阿来替尼、布加替尼和劳拉替尼联合使用与克唑替尼相比，心动过缓发生率相似（RR 0.77，95%CI 0.57-1.04）。所有 ALK 抑制剂（作为一个整体）引起的头晕（可能是心动过缓的症状）比标准化疗更多（RR 1.88，95%CI 1.44-2.44）。
与标准化疗相比，克唑替尼治疗 NSCLC 与心动过缓风险增加相关。克唑替尼和新型 ALK 抑制剂之间没有证据表明心动过缓风险存在差异。
