Proteinuria in Patients with Solid Tumors Treated with Ramucirumab: A Systematic Review and Meta-Analysis

BACKGROUND: We performed a systematic review and meta-analysis of the risk of proteinuria associated with ramucirumab. METHODS: Eligible studies included randomized phase II and III trials of patients with solid tumors on ramucirumab, describing events of all-grade and high-grade proteinuria. RESULTS: Our search strategy yielded 170 potentially relevant citations from PubMed/Medline, CENTRAL Cochrane database, ASCO and ESMO meeting libraries. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The relative risk (RR) of all-grade proteinuria was 3.31 (95% CI 2.48-4.42; p < 0.00001). Moreover, the RR of high-grade proteinuria was 5.28 (95% CI 2.32-12.01; p < 0.0001). CONCLUSIONS: Our meta-analysis has demonstrated that ramucirumab use is associated with an increased risk of all-grade and high-grade proteinuria. Early detection strategies should be employed in those patients to prevent the progression to more sinister renal disease.