Efficacy of PD-1/L1 inhibitors in brain metastases of non-small-cell lung cancer: pooled analysis from seven randomized controlled trials

Future Oncol. 2022 Jan;18(3):403-412. doi: 10.2217/fon-2021-0795. Epub 2021 Nov 17.

Abstract

Background: The efficacy of PD-1 or PD-L1 inhibitors in patients with brain metastases of non-small-cell lung cancer (BM-NSCLC) is inconclusive. Materials & methods: An electronic search was performed. Randomized controlled trials RCTs that compared the efficacy of PD-1- or PD-L1-inhibitor-based regimens with non-PD-1/L1 inhibitor regimens in patients with NSCLC and reported the data of subgroup patients with brain metastases were eligible for inclusion. The hazard ratios (HRs) for progression-free survival and overall survival were pooled in BM-NSCLC. Results: Seven RCTs with 472 BM-NSCLC cases are included. The pooled HRs indicated that PD-1 or PD-L1 inhibitor-based regimens reduced risk of disease progression by 44% and reduced risk of death of BM-NSCLC patients by 29% compared with non-PD-1/L1 inhibitor regimens. Conclusion: This meta-analysis indicates that PD-1 or PD-L1 inhibitors can reduce risk of both disease progression and death of patients with brain metastases of NSCLC, who have been pretreated with local therapies and/or are asymptomatic for the brain lesions.

Keywords: PD-1 inhibitor; PD-L1 inhibitor; brain metastases; immune checkpoint inhibitor; non-small-cell lung cancer.

Plain language summary

Lay abstracts The efficacy of PD-1 or PD-L1 inhibitors in patients with brain metastases of non-small-cell lung cancer (BM-NSCLC) is still inconclusive. We searched the electronic database of PubMed, Web of Science and Embase. All randomized controlled trials (RCTs) that compared the effectiveness of PD-1- or PD-L1-inhibitor-based treatment with non-PD-1/L1 inhibitor-based regimens in patients with NSCLC and reported the data of subgroup patients with brain metastases were eligible for inclusion. Finally, seven RCTs with 472 BM-NSCLC cases are included. All of these patients have been pretreated with local therapies and/or are asymptomatic for the brain lesions before joining the clinical trials. The pooled data of all trials indicated that PD-1- or PD-L1-inhibitor-based treatments reduced risk of disease progression of BM-NSCLC patients by 44% compared with non-PD-1/L1 inhibitor-based treatments. The results also showed that PD-1- or PD-L1-inhibitor-based treatments reduced risk of death of BM-NSCLC patients by 29% compared with non-PD-1/L1-inhibitor-based treatments. Our meta-analysis indicated that PD-1 or PD-L1 inhibitors can reduce risk of both disease progression and death in patients with brain metastases of NSCLC who have been pretreated with local therapies and/or are asymptomatic for the brain lesions.

Publication types

  • Meta-Analysis

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Disease Progression
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor