Incidence and relative risk of hemorrhagic events associated with ramucirumab in cancer patients: a systematic review and meta-analysis

The purpose of this study was to investigate the overall incidence and relative risk (RR) of hemorrhagic events in cancer patients treated with ramucirumab. 298 potentially relevant citations on ramucirumab from Pubmed, Web of Science and the Cochrane Database, as well as abstracts presented at conferences (all up to March 2016) were identified through our initial search. Only phase II and III prospective clinical trials of ramucirumab among cancer patients with toxicity records on hemorrhagic events were selected for final analysis. Data was extracted from the original studies by two independent reviewers. The overall incidence, RR, and 95% confidence intervals (CI) were calculated using fixed or random effects models according to the heterogeneity of the enrolled studies. The statistical analysis was performed by STATA version 11.0 (Stata Corporation, College Station, TX). 4963 patients with a variety of solid tumors from eleven eligible studies were selected into our analysis. The results demonstrated that the overall incidences of all-grade and high-grade hemorrhagic events in cancer patients were 27.6% (95% CI, 18.7-36.5%) and 2.3% (95% CI, 1.3-3.2%), respectively. The RR of hemorrhagic events of ramucirumab compared to control was significantly increased for low-grade (RR, 2.06; 95% CI, 1.85-2.29, p < 0.001), but not for high-grade (RR, 1.19, 95% CI, 0.80-1.76, p=0.39) hemorrhagic events. Hemorrhagic events associated with ramucirumab are modest and manageable while patients could continue to receive ramucizumab treatment to achieve their maximum clinical benefits.