Risk of gastrointestinal perforation in cancer patients receiving ramucirumab: a meta-analysis of randomized controlled trials

Purpose: Although existing evidence from clinical trials has demonstrated manifestation of gastrointestinal perforation with the use of ramucirumab, overall risks have yet to be reported. Therefore, we performed a meta-analysis of published randomized controlled trials (RCTs) to get a better understanding of the overall incidence and risk of gastrointestinal perforation associated with ramucirumab. Methods: The PubMed and Web of Science databases as well as abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant studies published up to 01 May 2015. Eligible studies included randomized trials of ramucirumab either alone or in combination with another agent compared with the control arm without ramucirumab and that reported gastrointestinal perforation event. Overall incidence, relative risk (RR) and 95% confidence intervals (CI) were computed using fixed-or random-effects models depending on the heterogeneity of the included studies. Results: A total of 4579 patients with a variety of solid malignancies from six RCTs were included in our meta-analysis. The incidence of gastrointestinal perforation related to ramucirumab was 1.5% (95% CI 1.1-2.1%) with a mortality of 29.8% (95% CI 14.9-50.7%). The RR of gastrointestinal perforation associated with ramucirumab was 2.56 (95% CI 1.29-5.09; P = 0.007). Conclusions: Treatment with the ramucirumab is associated with a significant increase in risk of gastrointestinal perforation in cancer patients.