Abstract

Immunocheckpoint inhibitors (ICIs) have become a standard pharmacological therapy in non‐small cell lung cancer (NSCLC). Because brain metastases (BMs) have historically been listed as exclusion criteria in previous clinical trials involving ICIs in advanced NSCLC, the survival benefit from ICI in NSCLC patients with BMs remains unclear. The National Cancer Database was queried for stage IV NSCLC patients with or without BMs between 2014 and 2015. Overall survival (OS) of stage IV NSCLC patients who received immunotherapy and that of stage IV NSCLC patients who did not receive immunotherapy were compared according to the presence or absence of BMs. Multivariable logistic analyses identified the clinical characteristics predictive of overall survival. A propensity score analysis was conducted with the aim of adjusting the potential biases arising from the clinical characteristics. This study included 42,512 patients with stage IV NSCLC; 11,810 patients with BMs and 30,702 patients without BMs. In univariate analysis, stage IV NSCLC patients with BMs treated with immunotherapy had a significantly longer OS than those without immunotherapy after propensity score matching (median OS: 12.8 vs 10.1 months, hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.72–0.89, p < 0.0001). Multivariable Cox modeling after propensity score matching confirmed the survival benefit from ICI for stage IV NSCLC patients with BMs (HR: 0.75, 95% CI: 0.67–0.83, p < 0.0001). The HR in NSCLC patients without BMs treated with ICI compared with those without ICI was 0.77 (95% CI: 0.73–0.82, p < 0.0001). Survival in stage IV NSCLC patients with BMs was significantly improved by ICI treatment at levels comparable to those without BMs using a retrospective database. ICI may be one of the promising treatment options for stage IV NSCLC patients with BMs. These findings should be validated in future prospective studies.

Highlights

  • Lung cancer is one of the most fatal malignancies worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer.[1]

  • A subgroup analysis of the Checkmate 057 trial reported that the hazard ratio (HR) for overall survival (OS) in NSCLC patients with brain metastasis (BM) treated with nivolumab compared with patients with BMs treated with docetaxel was 1.04 (95% confidence interval [CI], 0.62– 1.76)

  • A subgroup analysis of the OAK trial investigating 85 patients with BMs of total 850 patients (10.0%) showed that the HR for OS in NSCLC patients with BMs treated with atezolizumab in comparison to patients with BMs treated with docetaxel was 0.54.3

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Summary

| INTRODUCTION

Lung cancer is one of the most fatal malignancies worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer.[1]. According to a previous clinical trial investigating the efficacy of nivolumab in nonsquamous advanced NSCLC (Checkmate 057), only 68 patients with BMs of total 582 patients (11.7%) were included.[2] A subgroup analysis of the Checkmate 057 trial reported that the hazard ratio (HR) for overall survival (OS) in NSCLC patients with BMs treated with nivolumab compared with patients with BMs treated with docetaxel was 1.04 (95% confidence interval [CI], 0.62– 1.76). A subgroup analysis of the OAK trial investigating 85 patients with BMs of total 850 patients (10.0%) showed that the HR for OS in NSCLC patients with BMs treated with atezolizumab in comparison to patients with BMs treated with docetaxel was 0.54 (95% CI, 0.31–0.94).[3] the sample sizes of analyzed advanced NSCLC patients with BMs treated with ICIs in previous clinical trials were relatively small, and survival benefit from ICIs in such population remains unclear. The aim of this study was to clarify the survival benefit from ICIs in advanced NSCLC patients with BMs using the National Cancer Database (NCDB)

| MATERIALS AND METHODS
| RESULTS
| DISCUSSION
Findings
CONFLICTS OF INTEREST
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