title: Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.
abstract: We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients.
  
  
  
  We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, pembrolizumab; nivolumab; tremelimumab and atezolizumab. The authors extracted relevant information on participants, characteristics, treatment-related death and information on the methodology of the studies.
  
  
  
  After exclusion of ineligible records, 18 clinical trials were included in the analysis. The odds ratio for treatment-related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95% confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval 0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of treatment-related death.
  
  
  
  Analysis of our data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be associated with a higher risk of treatment-related death compared with control regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) do not cause the same risk. Clinicians have to be fully aware of these differential risks and council their patients appropriately.
authors.affiliation: Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; OncoCentrum Zurich, Gastrointestinal Tumor Center Zurich (GITZ), Zurich, Switzerland. Electronic address: omar.abdelrhman@med.asu.edu.eg.
authors.forename: O
authors.initials: O
authors.lastname: Abdel-Rahman
authors.affiliation: OncoCentrum Zurich, Gastrointestinal Tumor Center Zurich (GITZ), Zurich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Helbling
authors.affiliation: Surgical Center Zurich, Hirslanden Hospital, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: OncoCentrum Zurich, Swiss Tumor Immunology Institute (SwissTII), Zurich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Petrausch
authors.affiliation: OncoCentrum Zurich, Gastrointestinal Tumor Center Zurich (GITZ), Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Giryes
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mehrabi
authors.affiliation: Surgical Center Zurich, Hirslanden Hospital, Zurich, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Schöb
authors.affiliation: Department of Oncology, Center of Zug, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Mannhart
authors.affiliation: Surgical Center Zurich, Hirslanden Hospital, Zurich, Switzerland; Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Oweira
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018570:Risk Assessment
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human
keywords: Atezolizumab; ipilimumab; nivolumab; pembrolizumab; treatment-related death; tremelimumab