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Brain metastases and immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and
Haizhu Chen1, Yu Feng1, Yu Zhou1
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
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.
Insights
Immune checkpoint inhibitors (ICIs) show clinical activity in non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, BMs negatively impact progression-free and overall survival outcomes with ICIs, necessitating further treatment advancements.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Research
Background:
- The efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with brain metastases (BMs) is debated.
- This study investigates ICI efficacy in NSCLC patients with BMs and the impact of BMs on treatment outcomes.
Approach:
- A systematic meta-analysis was conducted across major databases (PubMed, Embase, Web of Science, Cochrane).
- Studies evaluating ICI efficacy against NSCLC BMs or the association between BMs and ICI outcomes were included.
- Key outcomes assessed included intracranial and systemic objective response rates (ORR) and disease control rates (DCR), progression-free survival (PFS), and overall survival (OS).
Key Points:
- Pooled intracranial ORR was 13% and icDCR was 50% for unselected patients with any BMs.
- For patients with PD-L1 ≥50%, pooled icORR was 68% and icDCR was 82%.
- Patients with BMs experienced inferior PFS and OS compared to those without BMs when treated with ICIs.
Conclusions:
- Immune checkpoint inhibitors demonstrate clinical activity in NSCLC patients with brain metastases.
- Further research and development of more effective treatments for NSCLC BMs are warranted.
