Risk of Selected Cardiovascular Toxicities in Patients With Cancer Treated With MEK Inhibitors: A Comparative Systematic Review and Meta-Analysis

Abstract

Purpose We conducted a literature-based meta-analysis of the risk of cardiovascular toxicities associated with MEK inhibitors. Methods Eligible trials included randomized phase II and III trials of patients with cancer who were given a mitogen activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (trametinib, selumetinib, or cobimetinib) and that described events of hypertension and decreased ejection fraction. Results Our search strategy yielded 300 potentially relevant citations from PubMed/MEDLINE, Google Scholar, and Cochrane Central Register of Controlled Trials. After ineligible studies were excluded, a total of 10 clinical trials were considered eligible for the meta-analysis. The relative risk for all grades of hypertension was 1.54 (95% CI, 1.02 to 2.32; P = .05), 1.85 (95% CI, 1.01 to 3.40; P = .05) for high-grade hypertension, and 4.92 (95% CI, 2.93 to 8.25; P < .001) for decreased ejection fraction. Subgroup analysis revealed no difference between trametinib and selumetinib for risk of hypertension. Conclusion Our meta-analysis demonstrated that MEK inhibitor–based treatment is associated with an increased risk of all-grade and high-grade hypertension and asymptomatic decrease in ejection fraction. Clinicians should be aware of this risk and perform regular assessment.