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

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.