Baseline Corticosteroid Use and Outcomes in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors, Stratified by Indication.

11184 Background: Baseline systemic corticosteroids are often prescribed to patients with non-small cell lung cancer (NSCLC) initiating immune checkpoint inhibitors (ICIs). Prior studies associating steroids with reduced ICI efficacy have largely treated steroid exposure as binary without accounting for indication. We evaluated outcomes following baseline steroid use by indication. Methods: We conducted a retrospective cohort study using TriNetX, a federated research network of de-identified electronic medical records. Using approximately 7,000-12,000 patients per stratum, NSCLC patients initiating ICIs were stratified by presence of systemic steroid prescriptions within 30 days prior to ICI initiation by indication: brain metastases (BM), pulmonary disease (PD), autoimmune disease (AI), and palliative indications (PI). In each stratum, steroid-exposed patients were compared with propensity-matched steroid-naive controls adjusting for demographics, non-brain metastases, comorbidities, substance use, and prior cancer treatments. Outcomes included mortality, ICU admission, and infection at 1 month. Results: Baseline steroid use was associated with worse 1 month outcomes in an indication dependent manner. Among patients receiving steroids for BM, mortality was higher compared with controls (8.75% vs 5.46%; HR 1.62, 95% CI 1.44-1.82; p < 0.001), as were ICU admission (5.06% vs 2.80%; RR 1.81, 95% CI 1.53-2.14; p < 0.001) and infection (6.81% vs 4.20%; RR 1.62, 95% CI 1.40-1.88; p < 0.001). Similarly, among patients receiving steroids for PI, steroid use was associated with increased mortality (9.68% vs 5.29%; HR 1.87, 95% CI 1.69-2.06; p < 0.001), ICU admission (4.83% vs 2.65%; RR 1.82, 95% CI 1.57-2.12; p < 0.001), and infection (7.50% vs 4.21%; RR 1.78, 95% CI 1.56-2.03; p < 0.001). In contrast, steroid use for PD or AI was not associated with increased mortality. PD was associated with higher ICU admission (3.35% vs 2.61%; RR 1.29, 95% CI 1.10-1.51; p = 0.0027) and infection (6.31% vs 4.23%; RR 1.49, 95% CI 1.31-1.70; p < 0.001), while AI was associated with increased ICU admission (3.63% vs 2.68%; RR 1.36, 95% CI 1.11-1.65; p = 0.0039) but not increased infection risk. These survival patterns persisted at longer follow-up, with higher mortality among patients with BM and PI at 6 months (BM HR 1.40, 95% CI 1.32-1.48; p < 0.001; PI HR 1.40, 95% CI 1.33-1.47; p < 0.001), 1 year (BM HR 1.40, 95% CI 1.33-1.47; p < 0.001; PI HR 1.36, 95% CI 1.31-1.42; p < 0.001), and 5 years (BM HR 1.30, 95% CI 1.24-1.35; p < 0.001; PI HR 1.32, 95% CI 1.27-1.37; p < 0.001), while no long-term survival decrement was observed for PD or AI. Conclusions: Baseline steroid use prior to ICI initiation is associated with increased early and long-term mortality in NSCLC in BM and PI but not PD and AI. Accounting for clinical indication is important to understand real-world ICI outcomes of patients using steroids.