Impact of concurrent systemic and inhaled corticosteroid use on clinical outcomes in advanced lung cancer patients receiving immune checkpoint inhibitors

TL;DR

Using systemic corticosteroids with immunotherapy for advanced lung cancer worsens outcomes, while inhaled corticosteroids do not.

Contribution

First study to compare the effects of concurrent systemic and inhaled corticosteroids on immunotherapy outcomes in lung cancer.

Findings

Systemic corticosteroids reduced progression-free and overall survival in patients receiving immunotherapy.

Inhaled corticosteroids showed no significant negative impact on clinical outcomes.

Starting systemic corticosteroids within 2 months of immunotherapy was linked to worse survival.

Abstract

Corticosteroids are frequently used during immune checkpoint inhibitor (ICI) treatment, especially in lung cancer patients with comorbidities. Previous studies suggest that systemic corticosteroids (SCS) hinder the effectiveness of ICIs, while the impact of inhaled corticosteroids (ICS) remains unclear. We aimed to examine the association between concurrent SCS and ICS on clinical outcomes in advanced lung cancer patients treated with ICIs.

This retrospective cohort study enrolled adults with advanced lung cancer who initiated ICIs between September 1 2016 and September 30 2023 at West China Hospital of Sichuan University. Exposure included concurrent SCS, ICS versus no steroid treatment. Clinical outcomes including overall survival (OS), progression-free survival (PFS), and tumor response were assessed. Time-dependent Cox regression models (treating SCS and ICS use as time-varying covariates) were applied to account for immortal-time bias.

Among 368 patients, 122 were SCS users, 51 were ICS users and 195 did not receive corticosteroids. SCS use was associated with inferior PFS (hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.40–2.84; p value < 0.001) and OS (HR 1.77; 95% CI, 1.25–2.51; p value = 0.001), whereas ICS use was not significantly associated with PFS (HR 1.35; 95% CI, 0.66–2.80; p value = 0.412) or OS (HR 1.48; 95% CI, 0.74–2.97; p value = 0.269). Subgroup and sensitivity analyses generally supported the robustness of these findings. In exploratory analyses restricted to SCS users, initiation of SCS within 2 months after ICI start was associated with worse survival.

This study suggests that concurrent SCS use may adversely affect the clinical outcomes of advanced lung cancer patients receiving immunotherapy, whereas ICS use did not appear to compromise ICI efficacy. These findings highlight the critical need for cautious consideration when combining ICIs with systemic corticosteroids and emphasize the importance of treating both cancer and lung comorbidity simultaneously.

The online version contains supplementary material available at 10.1186/s12931-025-03482-5.

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