title: Comparison of efficacy of immune checkpoint inhibitors (ICIs) between younger and older patients: A systematic review and meta-analysis.
abstract: BACKGROUND
  Immune checkpoint inhibitors (ICIs) rely on the presence of ongoing immune response to exert their antitumor effect. Little is known whether an age-related decline in immune function negatively influences antitumor response and in so doing diminishes the efficacy of ICIs in elderly subjects. We performed a meta-analysis to compare the efficacy of ICIs between younger and older patients.
  
  
  METHODS
  PubMed and the ASCO databases were searched up to September 2015. We included randomized controlled trials (RCTs) of ICIs (ipilimumab, tremelimumab, nivolumab and pembrolizumab) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.
  
  
  RESULTS
  A total of 5265 patients from nine RCTs of ICI were included. When patients are dichotomized into younger and older groups with an age cut-off of 65-70 years, ICIs improved OS in both younger (HR, 0.75; 95% CI, 0.68-0.82) and older (HR, 0.73; 95% CI, 0.62-0.87) groups. An improvement in PFS was observed in younger (HR, 0.58; 95% CI, 0.40-0.84) and older (HR, 0.77; 95% CI, 0.58-1.01) patients. Subgroup analyses according to ICI and tumor type showed a consistent survival benefit in both younger and older groups except for the subgroup of older patients treated in 4 trials of anti-programmed cell death protein-1 (PD-1) monoclonal antibody (HR, 0.86; 95% CI, 0.41-1.83).
  
  
  CONCLUSIONS
  A benefit in OS with ICIs was significant in both younger and older patients with a cut-off age of 65-70 years.
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, 170 Manning Drive, CB# 7305, Chapel Hill, NC 27599, USA. Electronic address: Tomohiro.Nishijima@unchealth.unc.edu.
authors.forename: Tomohiro F
authors.initials: TF
authors.lastname: Nishijima
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, 170 Manning Drive, CB# 7305, Chapel Hill, NC 27599, USA.
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, 170 Manning Drive, CB# 7305, Chapel Hill, NC 27599, USA; Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Shlomit S
authors.initials: SS
authors.lastname: Shachar
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, 170 Manning Drive, CB# 7305, Chapel Hill, NC 27599, USA.
authors.forename: Stergios J
authors.initials: SJ
authors.lastname: Moschos
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000145:classification / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000145:classification / Q000276:immunology / Q000494:pharmacology; D018572:Disease-Free Survival; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents
keywords: Age; Immune checkpoint inhibitor; Immunosenescence; Meta-analysis; Overall survival; Progression-free survival; Systematic review