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Immune checkpoint inhibitors for brain metastases in non-small-cell lung cancer: from rationale to clinical
Gang Xiao1, Zhiyuan Liu1, Xuan Gao2
1Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Abstract:
Brain metastases (BM) is common in non-small-cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors (ICIs) have gradually become a routine treatment for NSCLC BM patients. Currently, three PD-1 inhibitors (pembrolizumab, nivolumab and cemiplimab), one PD-L1 inhibitor (atezolizumab) and one CTLA-4 inhibitor (ipilimumab) have been approved for the first-line treatment of metastatic NSCLC. It is still controversial whether PD-L1, tumor infiltrating lymphocytes, and tumor mutation burden can be used as predictive biomarkers for immune checkpoint inhibitors in NSCLC patients with BM. In addition, clinical data on NSCLC BM were inadequate. Here, we review the theoretical basis and clinical data for the application of ICIs in the therapy of NSCLC BM.
Insights
Immune checkpoint inhibitors (ICIs) are increasingly used for non-small-cell lung cancer with brain metastases (NSCLC BM). This review examines their efficacy and predictive biomarkers for NSCLC BM treatment.
Area of Science:
- Oncology
- Immunotherapy
- Neurology
Background:
- Brain metastases (BM) are a frequent complication in non-small-cell lung cancer (NSCLC).
- Immune checkpoint inhibitors (ICIs) represent a significant advancement in NSCLC treatment, including cases with BM.
- Several ICIs targeting PD-1, PD-L1, and CTLA-4 are approved for metastatic NSCLC.
Purpose of the Study:
- To review the current theoretical basis for using ICIs in NSCLC BM.
- To analyze existing clinical data on the efficacy of ICIs in NSCLC patients with BM.
- To discuss the role and controversy surrounding predictive biomarkers for ICI therapy in NSCLC BM.
Main Methods:
- Literature review of preclinical studies and clinical trials.
- Analysis of data on approved ICIs (pembrolizumab, nivolumab, cemiplimab, atezolizumab, ipilimumab).
- Examination of potential predictive biomarkers including PD-L1 expression, tumor-infiltrating lymphocytes, and tumor mutation burden.
Main Results:
- ICIs have shown promise in treating NSCLC BM, becoming a routine option.
- Clinical data specifically for NSCLC BM treated with ICIs remain relatively limited.
- The predictive value of biomarkers like PD-L1, TILs, and TMB in this specific population is still under investigation and debated.
Conclusions:
- ICIs offer a valuable therapeutic strategy for NSCLC patients with brain metastases.
- Further research and robust clinical data are needed to optimize ICI use and biomarker selection in NSCLC BM.
- Clarifying the role of biomarkers will be crucial for personalized treatment approaches in NSCLC BM.
