In patients with advanced non–small-cell lung cancer (NSCLC) who are undergoing immunotherapy, real-world data suggests that steroid use is detrimental. Previous studies, on the other hand, contained heterogeneous cohorts of patients who were treated with a variety of immuno-oncology agents and combinations of chemotherapy and immuno-oncology agents.


A comprehensive clinicopathologic database of patients with NSCLC and programmed cell death ligand (1 >50%) treated with frontline pembrolizumab monotherapy was constructed in 14 centers in Switzerland, Greece, Spain, and Italy. A multivariate analysis adjusting for the established prognostic factors was performed using a Cox regression model. For the 265 eligible patients, the median age at diagnosis was 67 years, 66% were male, 90% were current or former smokers, 18% had had an Eastern Cooperative Oncology Group performance status of 2 or 3. Of the NSCLC subtypes, 64% were adenocarcinoma and 25% were squamous cells. Of the patients, 18% had had brain metastases at diagnosis and 24% had received steroids before or during pembrolizumab treatment. The median time to progression was 4.4 months with and 13.7 months without steroid use (hazard ratio [HR], 2.55; 95% CI, 1.69-3.85; log-rank P (< .001). The median survival was 22.5 months for the whole cohort, 7.7 months for the steroid group, and not reached for the non-steroid group (HR, 3.64; 95% CI, 2.34-5.68; log-rank P < .001). On multivariate analysis accounting for all prognostic variables, use of steroids was still independently associated with a high risk of progression (HR, 1.864; 95% CI, 1.179-2.949; P = .008) and death (HR, 2.292; 95% CI, 1.441-3.644; P < .001). Patients with programmed cell death ligand expression more than 50% and advanced NSCLC who received frontline pembrolizumab monotherapy, usage of any steroid during or before the treatment was associated with an 86% increase in the risk of progression and a 2.3-fold increase in the risk of death, even accounting for palliative indication-related bias. It includes the presence of central nervous system metastasis.