Risk of peripheral edema in cancer patients receiving MET inhibitors: a systematic review and meta-analysis

Although MET inhibitors are increasingly used in cancer treatment, the overall risk and key determinants of treatment-related peripheral edema remain insufficiently characterized. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) published until September 2025. Thirty-five RCTs involving 10,555 patients were included. Our results demonstrated that MET inhibitors were associated with a significantly increased risk of all-grade (RR 2.76, 95% CI 2.13-3.57; p < 0.00001; ARD, 14.1%; NND, 7) and high-grade peripheral edema (RR 2.67, 95% CI 1.74-4.09; p < 0.00001; ARD, 0.88%; NND, 113). Elevated risks were observed with tepotinib, savolitinib, amivantamab, and rilotumumab. Notably, monoclonal antibodies carried a higher edema risk than tyrosine kinase inhibitors, and combination therapy showed greater risk than monotherapy. The risk was also higher in lung cancer and in first-line settings. These findings provide comprehensive evidence for the risk profile of peripheral edema and support individualized monitoring in clinical practice.