title: Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis.
abstract: We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.
  
  
  
  Randomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation-defined subgroups. We used the fixed-effects inverse variance-weighted method to pool estimates of treatment efficacy. Statistical tests were two sided.
  
  
  
  In the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61-0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58-0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70-1.55, p < 0.81; treatment-mutation interaction p = 0.03).
  
  
  
  In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Cancer Care Centre, St. George Hospital, Sydney, Australia. Electronic address: chee.lee@ctc.usyd.edu.au.
authors.forename: Chee Khoon
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Cancer Care Centre, St. George Hospital, Sydney, Australia.
authors.forename: Johnathan
authors.initials: J
authors.lastname: Man
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; School of Medicine, The University of Norte Dame, Sydney, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Lord
authors.affiliation: Cancer Care Centre, St. George Hospital, Sydney, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Links
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia.
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.affiliation: Hong Kong Cancer Institute, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, People's Republic of China.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: Graduate Institute of Oncology, National Taiwan University and Department of Oncology, National Taiwan University Hospital, Taipei City, Republic of China.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutation; Immune checkpoint inhibitors; NSCLC; Predictive biomarker