Abstract
Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient’s NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.
Highlights
Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM)
The first evidence of this was reported in a phase 2 clinical trial in melanoma BM, which demonstrated a better response to immune checkpoint inhibitors (ICI) in patients who did not receive upfront steroids and were neurologically asymptomatic when compared to patients who received s teroids[12]
We investigated the impact of upfront steroids and neutrophil-to-lymphocyte ratio (NLR) on overall survival (OS) and progression-free survival (PFS) in a cohort of patients who began ICI after the diagnosis of NSCLCBM, a patient cohort with a universaly poor prognosis
Summary
Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs 17.9 months, p = .03) and intracranial PFS (5.0 vs 8.7 months, p = .045). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient’s NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI These results can inform clinicians about the impact of steroids in patients treated with ICI. Abbreviations NSCLCBM Non-small cell lung cancer brain metastases ICI Immune checkpoint inhibitors BM Brain metastases NLR Neutrophil to lymphocyte ratio WBRT Whole-brain radiation therapy.
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