Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Nov 25;1(2):73-82.
doi: 10.1200/JGO.2015.000802. eCollection 2015 Dec.

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

Omar Abdel-Rahman  1 , Hesham ElHalawani  1 , Hoda Ahmed  1
Affiliations
Review

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

Omar Abdel-Rahman et al. J Glob Oncol. .

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.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and contributions are found at the end of this article.The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Omar Abdel-RahmanNo relationship to discloseHesham ElHalawaniNo relationship to discloseHoda AhmedNo relationship to disclose

Figures

Figure 1
Figure 1
Flowchart of study selection procedure.
Figure 2
Figure 2
Forest plots of risk ratio of (A) all-grade hypertension associated with MEK inhibitors versus control and (B) high-grade hypertension associated with MEK inhibitors versus control; the size of squares corresponds to the weight of the study in the meta-analysis.
Figure 2
Figure 2
Continued
Figure 3
Figure 3
Forest plots of risk ratio of decreased ejection fraction associated with MEK inhibitors versus control.
Figure 4
Figure 4
Funnel plot for publication bias for all-grade hypertension. RR, risk ratio.
Figure 5
Figure 5
Funnel plot for publication bias for decreased ejection fraction. RR, risk ratio.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cooper ZA Reuben A Austin-Breneman J, etal: Does it MEK a difference? Understanding immune effects of targeted therapy Clin Cancer Res 21:3102–3104,2015 - PMC - PubMed
    1. Marzuka A Huang L Theodosakis N, etal: Melanoma treatments: Advances and mechanisms J Cell Physiol 230:2626–2633,2015 - PubMed
    1. Aggarwal C: Targeted therapy for lung cancer: Present and future Ann Palliat Med 3:229–235,2014 - PubMed
    1. Dossett LA, Kudchadkar RR, Zager JS: BRAF and MEK inhibition in melanoma Expert Opin Drug Saf 14:559–570,2015 - PubMed
    1. Falchook GS Lewis KD Infante JR, etal: Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: A phase 1 dose-escalation trial Lancet Oncol 13:782–789,2012 - PMC - PubMed