# Evaluating the Therapeutic Impact of Immune Checkpoint Inhibitors in the Management of Brain Metastases from Non-Small Cell Lung Cancer

**Authors:** Keren Rouvinov, Rashad Naamneh, Alexander Yakobson, Arina Soklakova, Wenad Najjar, Mahmoud Abu Amna, Mohnnad Asla, Ashraf Abu Jama, Nashat Abu Yasin, Mhammad Abu Juda, Sofyan Abu Freih, Yotam Malek, Walid Shalata

PMC · DOI: 10.3390/biomedicines14030566 · Biomedicines · 2026-03-02

## TL;DR

This paper reviews how immune checkpoint inhibitors affect brain metastases in non-small cell lung cancer patients, finding some promise but calling for more research.

## Contribution

The paper provides a narrative review of ICI efficacy in brain metastases, highlighting intracranial activity in specific patient subgroups.

## Key findings

- ICIs show significant intracranial activity in NSCLC patients with asymptomatic BMs and high PD-L1 expression.
- Current data is limited due to exclusion of patients with active or symptomatic BMs from clinical trials.
- More prospective studies are needed to validate ICI efficacy in treating BMs.

## Abstract

Background: Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), with an incidence rate of 25–40%. These metastases are associated with a poor prognosis. Although immune checkpoint inhibitors (ICIs) have revolutionized NSCLC treatment, their effectiveness against BMs remains not well-established. This is primarily because patients with active or symptomatic BMs have frequently been excluded from clinical trials. Methods: To address the lack of data, in this narrative review, we searched the available clinical guidelines and relevant studies. Databases, including PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, were searched for clinical studies published up to June 2025. The article included studies of NSCLC patients with BMs who were treated with ICIs and had reported central nervous system (CNS)-specific outcomes. Results: This article found that ICIs show significant intracranial activity. This activity is particularly notable in select NSCLC patients with asymptomatic BMs and high Programmed Death-Ligand 1 (PD-L1) expression. Conclusions: More research is needed to fully understand the efficacy of ICIs in treating BMs. Future prospective studies must include patients with active and symptomatic BMs to validate these findings and provide a clearer picture of ICI efficacy in this patient population.

## Linked entities

- **Proteins:** CD274 (CD274 molecule)
- **Diseases:** Non-small cell lung cancer (MONDO:0005233)

## Full-text entities

- **Genes:** CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}
- **Diseases:** BMs (MESH:D001932), NSCLC (MESH:D002289), metastases (MESH:D009362)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC13024657/full.md

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Source: https://tomesphere.com/paper/PMC13024657