title: Meta-analysis of randomized controlled trials for the incidence and risk of fatal adverse events in cancer patients treated with ipilimumab.
abstract: BACKGROUND
  Ipilimumab is a fully human immunoglobulin G1 monoclonal antibody that increases antitumor T-cell responses. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the risk of FAEs associated with ipilimumab.
  
  
  METHODS
  We searched PubMed, EMBASE, and ASCO meeting abstract up to September 2016 for RCT comparing ipilimumab with no ipilimumab on cancer patients. Incidence rates, relative risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using fixed- or random effects models. The primary end point was the association of ipilimumab with FAEs. Subgroup analyses were performed according to tumor type, concurrent therapy, and dose of ipilimumab.
  
  
  RESULTS
  A total of 5,466 patients from 10 RCTs were included. For patients receiving ipilimumab, the overall incidences of FAEs was 0.99% (95% CI: 0.48%-1.69%). Allocation to ipilimumab therapy increased the risk of FAEs (RR = 2.16, 95% CI, 1.03-4.54) significantly. Subgroup analyses reached statistical significance for prostate cancer, high dose of ipilimumab, and placebo as a control group. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  Compared with control or placebo, ipilimumab was associated with an increased risk of FAEs in cancer patients. As ipilimumab gains greater clinical use, practitioners must be aware of the risks associated with its use.
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Wu
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Guocheng
authors.initials: G
authors.lastname: Li
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Li
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: He
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Chen
authors.initials: C
authors.lastname: Su
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhao
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Zepeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.|b Department of Pharmacy , Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou , China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Qiu
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015994:Incidence; D000074324:Ipilimumab; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab
keywords: Ipilimumab; cancer patients; fatal adverse events; meta-analysis