title: Treatment-associated Fatigue in Cancer Patients Treated with Immune Checkpoint Inhibitors; a Systematic Review and Meta-analysis.
abstract: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints.
  
  
  
  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, nivolumab, pembrolizumab and tremelimumab. The authors extracted relevant information on participants(') characteristics, all-grade and high-grade fatigue and information on the methodology of the studies.
  
  
  
  In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade fatigue for CTLA-4 inhibitors was 1.23 (95% confidence interval 1.07, 1.41; P = 0.003) and for high-grade fatigue was 1.72 (95% confidence interval 1.26, 2.33; P = 0.0005). Moreover, the odds ratio for all-grade fatigue for PD-1 inhibitors was 0.72 (95% confidence interval 0.62, 0.84; P < 0.0001) and for high-grade fatigue was 0.36 (95% confidence interval 0.23, 0.56; P < 0.00001).
  
  
  
  The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade fatigue compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade fatigue compared with control regimens.
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: Department of HPB and Liver Transplantation, Rajhy Liver Hospital, Assiut University, Assiut, Egypt.
authors.forename: A
authors.initials: A
authors.lastname: Zidan
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; D005221:Fatigue / Q000139:chemically induced*; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012306:Risk
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Fatigue; ipilimumab; nivolumab; pembrolizumab; tremelimumab