{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for non-small cell lung cancer (NSCLC), but immune-related adverse events (irAEs) and their management remain key challenges. Real-world evidence on the toxicity and mortality associated with ICIs in NSCLC, particularly in patients without pre-existing autoimmune disease, is limited. We conducted a large-scale comparative analysis to evaluate the incidence of irAEs, steroid use, and mortality among ICI-treated versus non-ICI-treated NSCLC patients using real-world data. 1 Methods We performed a retrospective cohort study using the TriNetX Global Collaborative Network. 2 Adults (≥18 years) with NSCLC (ICD-10: C34) were included. Patients with prior autoimmune disease (e.g., SLE, RA, IBD, psoriasis) were excluded. Cohort 1 included patients who received at least one ICI (e.g., nivolumab, pembrolizumab); Cohort 2 included those who did not. Propensity score matching (1:1) was applied to balance baseline characteristics. Patients were included if they initiated treatment within the past 20 years, and outcomes were assessed over a 12-month period. These included mortality, pneumonitis, colitis, thyroiditis, hepatitis, hypophysitis, neurologic irAEs, steroid use, and hospitalization. Risk analyses, odds ratios, and Kaplan-Meier survival curves were generated. Patients with prior events were excluded from individual outcome analyses.Results After matching, 35,239 patients were included per group. ICI-treated patients had higher risks of:Mortality: 26.9% vs. 20.8% (OR 1.40, 95% CI 1.35–1.45; p<0.001)Colitis: 3.0% vs. 1.3% (OR 2.32, p<0.001)Pneumonitis: 15.5% vs. 13.3% (OR 1.20, p<0.001)Thyroiditis: 1.1% vs. 0.1% (OR 10.76, p<0.001)Hepatitis: 1.1% vs. 0.3% (OR 3.43, p<0.001)Hypophysitis: 0.6% vs. 0.3% (OR 1.75, p<0.001)Neurologic irAEs: 4.3% vs. 1.8% (OR 2.46, p<0.001)Steroid use: 64.1% vs. 30.1% (OR 4.15, p<0.001)Hospitalization: 0.9% vs. 0.0% (p<0.001)Kaplan-Meier survival probability at one year was lower in the ICI group (68.7% vs. 74.6%; HR 1.22, p<0.001) (figure 1).Conclusions While increased irAE risk with ICIs is anticipated, this real-world study quantifies the scope and clinical consequences. The >10-fold increase in thyroiditis, doubled neurologic irAEs, and elevated mortality underscore the importance of refining patient selection and monitoring. These findings call for careful risk-benefit assessment, especially in older adults or those with comorbidities, and support the development of early toxicity mitigation strategies in routine NSCLC practice.Acknowledgements This study was conducted using de-identified data from the TriNetX platform. The authors did not receive external funding.References Murff HJ, Roumie CL, Greevy RA, et al. Data collection for comparative effectiveness research: defining the learning health system. Med Care. 2014;52(12 Suppl 3):S12-S20.TriNetX. Real-world data network for clinical research. TriNetX White Paper. 2023. Available at: https://www.trinetx.com Ethics Approval This study was conducted using de-identified data from the TriNetX Global Collaborative Network. The use of this data for research purposes is considered exempt from institutional review board (IRB) approval under U.S. federal regulation 45 CFR §46.104(d)(4), as no identifiable private information was used.Consent Not applicable. This study used de-identified, aggregate electronic health record data from the TriNetX network. No individual patient-level consent was required.",
  "authors": [
    {
      "affiliations": [
        "UPMC, Harrisburg, PA, USA"
      ],
      "name": "Fatma B Yilmaz"
    },
    {
      "affiliations": [
        "UPMC, Harrisburg, PA, USA"
      ],
      "name": "Silvana Ribeiro Papp"
    },
    {
      "affiliations": [
        "JFK University Medical Center Edison, New Jersey, NJ, USA"
      ],
      "name": "Salih E Akgun"
    },
    {
      "affiliations": [
        "UPMC, Harrisburg, PA, USA"
      ],
      "name": "Anas Atrash"
    }
  ],
  "title": "1077 Real-world impact of immune checkpoint inhibitors on immune-related adverse events and mortality in patients with non-small cell lung cancer",
  "uid": "cc64a3b4-74cb-5632-947e-0cfea4311313"
}