Risk of peripheral edema in cancer patients treated with MEK inhibitors: a systematic review and meta-analysis of clinical trials

Abstract

Background: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors.

Materials and methods: The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau², Chi², and I² analyses.

Results: A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98–4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66–5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved.

Conclusion: This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.

Keywords:

• Trametinib
• selumetinib
• peripheral edema
• MEK inhibitor
• meta-analysis

Transparency

Declaration of funding

This study was funded by the Beijing Municipal Administration of Hospitals ‘Ascent Plan, code: DFL20150901.

Declaration of financial/other relationships

The authors report no conflicts of interest. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr Marc Fisher, Dr Yang, Ye and Dr Bo, Li for review and discussions.