Risks of Cardiovascular Toxicities Associated with ALK Tyrosine Kinase Inhibitors in Patients with Non-Small-cell Lung Cancer: a Meta-Analysis of Randomized Control Trials.

BackgroundAnaplastic lymphoma kinases (ALK) tyrosine kinase inhibitors (TKIs) are effective and safe targeted therapies used in advanced ALK-positive non-small cell lung cancers (NSCLC). However, ALK-TKIs associated cardiovascular toxicities in patients with ALK-positive NSCLCremain incompletely characterized. We conducted the first meta-analysis to investigate this.Research design and methodsTo determine the cardiovascular toxicities associated with these agents, we carried out a meta-analysis comparing ALK-TKIs with chemotherapy and a meta-analysis comparing crizotinib with other ALK-TKIs. Statistical analysis was conducted to calculate the RRs and 95% confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of the included studies.ResultsA total of 11 studies (2855 patients) were included. ALK-TKIs ranked to have more severe cardiovascular toxicities than chemotherapy (RR 5.03, 95% CI 1.97-12.84, P = 0.0007) . Compared with other ALK-TKIs, increased risks of cardiac disorders and VTEs associated with crizotinib were found (cardiac disorders RR 1.75, 95% CI 1.07-2.86, P = 0.03; risk of VTEs RR 3.97, 95% CI 1.69-9.31, P = 0.002; respectively).ConclusionALK-TKIs were associated with higher risks of cardiovascular toxicities. Special attention should be given to the risks of cardiac disorders and VTEs related to crizotinib therapy.