{
  "abstract": "Background Sex-based differences in immune response are well established, but whether men and women derive comparable benefit from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) remains uncertain. This systematic review and meta-analysis aimed to investigate sex-related differences in effectiveness of ICI for the treatment of advanced NSCLC.Methods A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted to compare overall survival (OS) and progression-free survival (PFS) between men and women treated with ICIs versus chemotherapy for stage III–IV NSCLC. Eligible studies compared programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) inhibitors with chemotherapy and reported sex-specific OS and/or PFS outcomes. HRs were pooled using random-effects models, and secondary analyses incorporated updated follow-up data where available.Results 55 RCTs comprising 28 550 adults (71.6% men; 28.4% women) were included. ICIs significantly improved OS in both men (HR=0.75, 95% CI 0.72 to 0.78) and women (HR=0.81, 95% CI 0.76 to 0.86; p=0.17 for difference). However, PFS benefits favoured men (HR=0.62, 95% CI 0.59 to 0.65) compared with women (HR=0.76, 95% CI 0.70 to 0.81; p=0.005). In analyses using the most recent follow-up data, women showed lower ICI effectiveness for both OS (p=0.043) and PFS (p=0.003).Conclusions ICIs confer similar OS benefits in men and women with advanced NSCLC, but women show shorter PFS, particularly in PD-L1-positive and monotherapy settings. Further research should clarify the biological and clinical factors underlying these differences and ensure balanced representation and equitable evaluation in future trials.PROSPERO registration number CRD42024451670.",
  "authors": [
    {
      "affiliations": [
        "Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"
      ],
      "name": "Erick Suazo-Zepeda"
    },
    {
      "affiliations": [
        "Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"
      ],
      "name": "Grietje G Talen"
    },
    {
      "affiliations": [
        "Medical Library, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands",
        "Medical Library, University of Groningen, Groningen, The Netherlands"
      ],
      "name": "Sjoukje van der Werf"
    },
    {
      "affiliations": [
        "Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"
      ],
      "name": "Jeroen T J N Hiltermann"
    },
    {
      "affiliations": [
        "Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"
      ],
      "name": "Willemijn Maas"
    },
    {
      "affiliations": [
        "Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"
      ],
      "name": "Geertruida H De Bock"
    },
    {
      "affiliations": [
        "Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands",
        "Institute for Diagnostic Accuracy, Groningen, The Netherlands",
        "Department of Respiratory Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands"
      ],
      "name": "Marjolein A Heuvelmans"
    }
  ],
  "title": "Sex-based differences in effectiveness of immune checkpoint inhibitors in the treatment of advanced non-small-cell lung cancer: systematic review and meta-analysis",
  "uid": "cec844fd-64b3-5324-83a9-1b89842ed4ce"
}