Impact of glucocorticoid administration on therapeutic outcomes of immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis
Bibliographic record
Abstract
Background Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced NSCLC, yet concurrent glucocorticoid use raises concerns due to immunosuppressive effects. Evidence regarding the prognostic impact of glucocorticoids in this setting remains inconsistent. This study aimed to systematically evaluate the association between glucocorticoid use and survival outcomes in NSCLC patients receiving ICIs, with particular attention to timing of administration. Methods A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted up to December 18, 2024, with no language restrictions. Eligible studies enrolled adult NSCLC patients treated with ICIs, stratified by glucocorticoid exposure, and reported overall survival (OS), progression-free survival (PFS), or objective response rate (ORR). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using fixed- or random-effects models depending on heterogeneity. Study quality was appraised with the Newcastle–Ottawa Scale, and evidence certainty was evaluated using GRADE. Subgroup analyses were conducted to assess the impact of glucocorticoid timing (pre-ICI, at initiation, and post-ICI) on survival outcomes. Results Fifteen studies involving 5,950 patients were included. Glucocorticoid use was significantly associated with inferior outcomes. The pooled HR for PFS was 1.44 (95% CI, 1.15–1.73; p < 0.001; I2 = 77.7%), and for OS was 1.58 (95% CI, 1.24–1.93; p < 0.001; I2 = 84.2%). Subgroup analysis demonstrated that post-ICI glucocorticoid administration was strongly associated with poorer survival (PFS: HR = 1.98, 95% CI, 1.51–2.62; OS: HR = 2.28, 95% CI, 1.61–3.41; both p < 0.001), while pre-ICI use showed no significant effect (PFS: HR = 1.21, 95% CI, 0.85–2.01; OS: HR = 1.31, 95% CI, 0.69–2.28). Funnel plots and Egger’s regression test indicated no significant publication bias (PFS: p = 0.42; OS: p = 0.37). Evidence certainty for both OS and PFS was rated as moderate. Conclusion In NSCLC patients receiving ICI therapy, glucocorticoid use might be associated with significantly poorer progression-free and overall survival, particularly when administered after the initiation of ICIs. Further research is warranted to clarify the timing and dosing parameters that could minimize potential negative effects on ICI efficacy. Systematic review registration PROSPERO, identifier CRD420251156730, available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251156730 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.027 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.039 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".