title: Incidence and relative risk of hemorrhagic events associated with ramucirumab in cancer patients: a systematic review and meta-analysis.
abstract: 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.
authors: Department of Pathology, Anhui Cancer Hospital, Hefei, Anhui, China.
authors: Rui
authors: R
authors: Tian
authors: Department of Pathology, Anhui Cancer Hospital, Hefei, Anhui, China.
authors: Hong
authors: H
authors: Yan
authors: Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Fei
authors: F
authors: Zhang
authors: Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.|State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China.|Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Peng
authors: P
authors: Sun
authors: Department of Head, Neck and Breast Surgery, Anhui Cancer Hospital, Hefei, Anhui, China.
authors: Xucai
authors: X
authors: Zheng
authors: Department of Gynaecology and Obstetrics, Anhui Provincial Hospital, Hefei, Anhui, China.
authors: Yi
authors: Y
authors: Zhu
authors: Department of Gynaecology and Obstetrics, Anhui Provincial Hospital, Hefei, Anhui, China.
authors: Qing
authors: Q
authors: Wang
authors: Department of Pathology, Anhui Cancer Hospital, Hefei, Anhui, China.
authors: Jie
authors: J
authors: He
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002681:China / Q000453:epidemiology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D012307:Risk Factors; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000096662:Ramucirumab
keywords: VEGF; VEGFR; bleeding; hemorrhagic events; ramucirumab