Source: Cancer Research Communications
Baseline corticosteroid use, particularly at high doses (>30 mg prednisone equivalent), significantly reduces the efficacy of immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) patients and serves as the strongest independent predictor of poor outcomes. Oncologists should exercise caution when interpreting blood-based immune biomarkers in steroid-treated patients, as steroids impair T-cell maturation and confound predictive markers.
Study Design & Population
- Study type: Retrospective cohort analysis with preclinical validation
- Sample size: 277 NSCLC patients receiving ICI therapy at two academic centers
- Key characteristics: 21 patients (8%) on baseline steroids for ≥12 weeks
- Institutions: University of Southern California (n=189) and Roswell Park Comprehensive Cancer Center (n=88)
Key Findings
- Overall response rate: Lower in steroid users versus non-users (specific rates not provided)
- Progression-free survival: 3.2 vs 10.7 months (USC cohort) and 3.0 vs 6.6 months (RPCCC cohort)
- Overall survival: 7.7 vs 21.0 months (USC) and 3.7 vs 16.4 months (RPCCC)
- Independent risk factor: Steroid use was the only significant predictor in multivariate analysis across both cohorts
- Mechanism: Steroids inhibit T-cell maturation and reduce CX3CR1+CD8+ T cell frequency
- Biomarker impact: Neutrophil-to-lymphocyte ratio lost prognostic value in steroid-treated patients
Clinical Implications
- Consider postponing ICI initiation until steroids can be discontinued or tapered to lowest effective dose
- Standard blood-based biomarkers (NLR, CX3CR1+ CD8+ T cells) may be unreliable in steroid-treated patients
- High-dose steroids (>30 mg prednisone equivalent) pose greater risk than lower doses
- Preclinical data suggests stopping steroids at ICI initiation may restore efficacy
Limitations
- Small steroid cohort: Only 8% of patients on baseline steroids
- Incomplete biomarker data for NLR and CX3CR1+ CD8+ T cells
- Limited dose analysis: Small medium-dose group (7.5-30 mg prednisone equivalent)
- Single mouse model used for preclinical validation
- 30-day exposure window: Analysis limited to steroid use within 30 days of ICI initiation
- Higher brain metastases rate (24.2%) than prior studies may confound results
