The corticosteroid timing paradox in immune checkpoint inhibitor–treated solid tumors and its association with overall survival: A TriNetX retrospective cohort study.

Abstract

11140 Background: Systemic corticosteroids are frequently used in patients receiving immune checkpoint inhibitors (ICIs) for symptom control and management of immune-related adverse events (irAEs). However, corticosteroids may impair antitumor immunity, and the impact of timing of corticosteroid exposure relative to ICI initiation on survival outcomes remains incompletely defined. We evaluated the association between corticosteroid timing and overall survival (OS) in a large real-world cohort of ICI-treated solid tumor patients. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, including adult patients (≥18 years) with solid tumors treated with ICIs. Patients were stratified based on systemic corticosteroid exposure into three groups: baseline use (−30 to 0 days before ICI initiation), early intercurrent use (1–56 days after ICI initiation), and late intercurrent use (57–180 days after ICI initiation). Patients without corticosteroid exposure served as controls. The primary outcome was overall survival (OS). Kaplan–Meier analysis and Cox proportional hazards models were used to estimate survival outcomes and hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 43,282 ICI-treated solid tumor patients were included. Baseline corticosteroid use was associated with significantly worse OS compared with no corticosteroid exposure (median OS 564 vs 900 days; HR 1.32, 95% CI 1.28–1.35; p < 0.0001). Similarly, early intercurrent corticosteroid use was associated with inferior OS (median OS 543 vs 907 days; HR 1.35, 95% CI 1.32–1.39; p < 0.0001). In contrast, late intercurrent corticosteroid use was not associated with a survival detriment compared with controls (median OS 617 vs 650 days; HR 0.99, 95% CI 0.97–1.02; p = 0.60). Conclusions: In this large real-world analysis, systemic corticosteroid exposure prior to or early during ICI therapy was associated with significantly worse overall survival, whereas corticosteroid use later during treatment did not adversely impact survival. These findings support a corticosteroid timing paradox, suggesting that early immunosuppression may impair ICI efficacy, while later corticosteroid use—often for irAE management—may be oncologically safe. Prospective studies are needed to further define optimal corticosteroid timing and indications in ICI-treated patients.