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Meta-Analysis
. 2022 Dec;71(12):3071-3085.
doi: 10.1007/s00262-022-03224-2. Epub 2022 Jun 1.

Brain metastases and immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis

Haizhu Chen #  1 , Yu Feng #  1 , Yu Zhou #  1 , Yunxia Tao  1 , Le Tang  1 , Yuankai Shi  2
Affiliations
Meta-Analysis

Brain metastases and immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis

Haizhu Chen et al. Cancer Immunol Immunother. 2022 Dec.

Abstract

Background: The use of immune checkpoint inhibitors (ICIs) for brain metastases (BMs) from non-small cell lung cancer (NSCLC) remains debatable. This study aimed to explore the efficacy of ICIs for NSCLC with BMs. We also evaluated the effect of BMs on outcomes of ICIs.

Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane databases was conducted to identify studies where the efficacy of ICIs against BMs from NSCLC, or the association between BMs and outcomes of ICIs were evaluated. Outcomes included intracranial objective response rate (icORR), intracranial disease control rate (icDCR), systemic ORR and DCR.

Results: Overall, 33 studies were included in this meta-analysis. The pooled icORR was 13% (95%CI 6-23%) and icDCR was 50% (95%CI 40-63%) for programmed cell death-ligand 1 (PD-L1) unselected patients with any BMs. For active BMs, pooled icORR was 15% (95%CI 6-28%) and icDCR was 47% (95% CI 36-57%). For PD-L1 ≥ 50% patients with any BMs, pooled icORR and icDCR were 68% (95%CI 57-80%) and 82% (95%CI 73-92%), respectively. Additionally, pooled systemic ORR and DCR for any BMs were 22% (95%CI 15-30%) and 41% (95%CI 18-67%), respectively. Patients with BMs had inferior progression-free survival (HR 1.19, 95%CI 1.07-1.33, P = 0.0016) and overall survival (HR 1.14, 95%CI 1.03-1.25, P = 0.011) when applying ICIs compared to those without BMs. However, no significant difference in systemic ORR between patients with and without BMs was observed (OR 0.94, 95%CI 0.72-1.20, P = 0.629).

Conclusion: ICIs may be clinically active in NSCLC patients with BMs. More effective treatments for BMs from NSCLC are needed.

Keywords: Brain metastases; Immune checkpoint inhibitor; Meta-analysis; Non-small cell lung cancer.

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Conflict of interest statement

All the authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart of inclusion and exclusion procedure
Fig. 2
Fig. 2
Forest plot of the pooled icORR. A The pooled icORR for PD-L1 unselected patients with any BMs; B The pooled icORR for PD-L1 TPS ≥ 50% patients with any BMs; C The pooled icORR for PD-L1 unselected patients with active BMs. icORR, intracranial objective response rate; PD-L1, programmed cell death-ligand 1; BMs, brain metastases; TPS, tumor proportion score
Fig. 3
Fig. 3
Forest plot of the pooled icDCR. A The pooled icDCR for PD-L1 unselected patients with any BMs; B The pooled icDCR for PD-L1 TPS ≥ 50% patients with any BMs; CThe pooled icDCR for PD-L1 unselected patients with active BMs. icDCR, intracranial disease control rate; PD-L1, programmed cell death-ligand 1; BMs, brain metastases; TPS, tumor proportion score
Fig. 4
Fig. 4
Forest plot of the pooled systemic response. A The pooled systemic disease control rate for patients with any BMs; B The pooled systemic objective response rate for patients with any BMs; C The systemic objective response rate for PD-L1 TPS ≥ 50% patients with any BMs. BMs, brain metastases; PD-L1, programmed cell death-ligand 1; TPS, tumor proportion score
Fig. 5
Fig. 5
Meta-analysis of the association between brain metastases (BMs) and survival outcomes in patients treated with immune checkpoint inhibitor (BMs vs. non-BMs). A Progression-free survival; B Overall survival
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