title: Efficacy of Tumor Vaccines and Cellular Immunotherapies in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.
abstract: Programmed cell death protein-1- checkpoint blockers have recently been approved as second-line treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, only a subgroup of patients responds and shows long-term survival to these therapies. Tumor vaccines and cellular immunotherapies could synergize with checkpoint blockade, but which of these treatments is most efficacious is unknown. In this meta-analysis, we assessed the efficacy of tumor vaccination and cellular immunotherapy in NSCLC.
  
  
  
  We searched for randomized controlled trials (RCTs) investigating cellular immunotherapy or vaccines in NSCLC. We used random effects models to analyze overall survival (OS) and progression-free survival (PFS), expressed as hazard ratios (HRs), and differences in time (months). The effect of immunotherapy type, disease stage, tumor histology, and concurrent chemotherapy was assessed using subgroup analysis and meta-regression. All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
  
  
  
  We identified 18 RCTs that matched our selection criteria; these included a total of 6,756 patients. Immunotherapy extended NSCLC survival and PFS, expressed as HR (OS: HR, 0.81, 95% CI, 0.70 to 0.94, P = .01; PFS: HR, 0.83, 95% CI, 0.72 to 0.95, P = .006) and month difference (OS: difference, 5.43 months, 95% CI, 3.20 to 7.65, P < .005; PFS: difference, 3.24 months, 95% CI, 1.61 to 4.88, P < .005). Cellular therapies outperformed tumor vaccines (OS as HR: P = .005, month difference: P < .001; PFS as HR: P = .001, month difference: P = .004). There was a benefit of immunotherapy in low-stage compared with high-stage NSCLC and with concurrent administration of chemotherapy only in one of four outcome measures evaluated (PFS in months: P = .01 and PFS as HR: P = .031, respectively). There was no significant effect of tumor histology on survival or PFS.
  
  
  
  Tumor vaccines and cellular immunotherapies enhanced OS and PFS in NSCLC. Cellular immunotherapy was found to be more effective than tumor vaccination. These findings have implications for future studies investigating combination immunotherapy in NSCLC.
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands.
authors.forename: Floris
authors.initials: F
authors.lastname: Dammeijer
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands.
authors.forename: Lysanne A
authors.initials: LA
authors.lastname: Lievense
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands.
authors.forename: G D Marijn
authors.initials: GD
authors.lastname: Veerman
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands.
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Hegmans
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands.
authors.forename: Lidia R
authors.initials: LR
authors.lastname: Arends
authors.affiliation: Floris Dammeijer, Lysanne A. Lievense, G.D. Marijn Veerman, Henk C. Hoogsteden, Joost P. Hegmans, Joachim G. Aerts, and Lidia R. Arends, Erasmus Medical Center, Rotterdam, The Netherlands; and Joachim G. Aerts, Amphia Hospital, Breda, The Netherlands. j.aerts@erasmusmc.nl.
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Aerts
mesh_terms: D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018572:Disease-Free Survival; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines