The Effect of Asymptomatic and/or Treated Brain Metastases on Efficacy of Immune Checkpoint Inhibitors in Metastatic Non-Small Cell Lung Cancer: A Meta-Analysis.

Sihan Li,Tingting Liu,Hongwei Zhang,Jun Chen,Jun Dang

doi:10.3389/fonc.2021.702924

Abstract

BackgroundTo assess the effect of asymptomatic and/or treated brain metastases (BMs) on the efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC).Patients and MethodsPubMed, Embase, Cochrane Library, Web of Science, and recent meetings were searched for randomized controlled trials (RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS).ResultsSeventeen articles reporting 15 RCTs with 10,358 patients (1,199 with and 9,159 without BMs) were eligible. ICIs were associated with longer OS and PFS than those in chemotherapy either in patients with (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51–0.82 and HR, 0.60; 95% CI, 0.45–0.79) or without BMs (HR, 0.74; 95% CI, 0.70–0.78 and HR, 0.70; 95% CI, 0.57–0.86); no significant difference in the pooled HRs for OS (Pinteraction = 0.29) and PFS (Pinteraction = 0.37) was observed between the two patient populations. Subgroup analyses revealed that either ICI monotherapy or combination therapy significantly improved OS and PFS compared with those in chemotherapy both for patients with and without BMs. Superior OS benefit from ICI combination therapy than that in monotherapy was observed in patients with BMs (HR, 0.49 vs. 0.81, Pinteraction = 0.005) but not in patients without BMs (HR, 0.71 vs. 0.76, Pinteraction = 0.27).ConclusionThere was no compelling statistical evidence that the efficacy of ICIs in metastatic NSCLC was modified by the presence of asymptomatic and/or treated BMs. Patients with BMs were likely to obtain more OS benefit from ICI combination therapy than that from monotherapy.

Highlights

Brain metastases (BMs) are a common complication of advanced lung cancer with poor prognosis, occurring in 20% to 40% of patients with non-small cell lung cancer (NSCLC) [1]
Whether the presence of asymptomatic and/or treated can decrease the survival benefit from immune checkpoint inhibitors (ICIs) remains uncertain. This is a comprehensive metaanalysis focusing on the effect of asymptomatic and/or treated BMs on the efficacy of ICIs in metastatic NSCLC
This study included 15 randomized-controlled trial (RCT) involving 10358 patients (1,199 with and 9,159 without BMs). It showed that ICIs were associated with longer overall survival (OS) and progression-free survival (PFS) than that in CT either in patients with or without BMs; no significant differences in the pooled hazard ratios (HRs) for OS (HR, 0.65 vs. 0.60; Pinteraction = 0.29) and PFS (HR, 0.74 vs. 0.70; Pinteraction = 0.37) were observed, suggesting a comparable efficacy of ICIs for the two patient populations

Summary

Introduction

Brain metastases (BMs) are a common complication of advanced lung cancer with poor prognosis, occurring in 20% to 40% of patients with non-small cell lung cancer (NSCLC) [1]. Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape of metastatic NSCLC patients lacking EGFR or ALK alteration. In CheckMate-057 [9], -078 [10], and a pooled analysis of KEYNOTE-010 and -024 and -042 trials [20], patients with baseline asymptomatic or treated BMs had similar OS with ICIs or chemotherapy (CT). CheckMate-227 [11, 12], -9LA [13], and a pooled analysis of KEYNOTE-021 and -189 and -407 trials [21] showed that ICIs significantly improved survival compared with that in CT. To assess the effect of asymptomatic and/or treated brain metastases (BMs) on the efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC)

Methods

Results

Conclusion