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Anaplastic 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. To 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. A 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). ALK-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.

expert opinion on drug safety

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