Impact of glucocorticoid administration on therapeutic outcomes of immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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; <i>p</i> < 0.001; I² = 77.7%), and for OS was 1.58 (95% CI, 1.24-1.93; <i>p</i> < 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 <i>p</i> < 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: <i>p</i> = 0.42; OS: <i>p</i> = 0.37). Evidence certainty for both OS and PFS was rated as moderate.<h4>Conclusion</h4>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.<h4>Systematic review registration</h4>PROSPERO, identifier CRD420251156730, available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251156730.