Abstract

Brain metastases remain a critical issue in the management of non-small cell lung cancer (NSCLC) because of the high frequency and poor prognosis, with survival rates often measured in just months. The local treatment approach remains the current standard of care, but management of multiple asymptomatic brain metastases always involves systemic therapy. Given that anti-angiogenic agents and immune checkpoint inhibitors (ICIs) both target the tumor microenvironment (TME), this combination therapy has become a promising strategy in clinical practice. Increasing number of preclinical and clinical studies have shown remarkable anti-tumor activity of the combination therapy, but the efficacy in brain metastases is unclear due to the strict selection criteria adopted in most clinical trials. This review briefly summarizes the potential synergistic anti-tumor effect and clinical development of the combination of anti-angiogenic agents and ICIs in NSCLC brain metastases, and discusses the existing challenges and problems.

Highlights

  • Lung cancer is one of the most common malignant tumors and the leading cause of cancer-related mortality worldwide [1, 2]

  • Given recent advances in immunotherapy, emerging clinical evidence suggests that immune checkpoint inhibitors (ICIs) have anti-tumor effects in brain metastases from non-small cell lung cancer (NSCLC)

  • The OAK study showed that the hazard ratio (HR) for overall survival (OS) with atezolizumab vs. docetaxel was 0.73 for the overall population, 0.74 for patients without brain metastases, and 0.54 for patients with brain metastases [69]

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Summary

Frontiers in Oncology

Anti-Angiogenic Agents in Brain Metastases From Non-Small Cell Lung Cancer. Brain metastases remain a critical issue in the management of non-small cell lung cancer (NSCLC) because of the high frequency and poor prognosis, with survival rates often measured in just months. Given that anti-angiogenic agents and immune checkpoint inhibitors (ICIs) both target the tumor microenvironment (TME), this combination therapy has become a promising strategy in clinical practice. Increasing number of preclinical and clinical studies have shown remarkable anti-tumor activity of the combination therapy, but the efficacy in brain metastases is unclear due to the strict selection criteria adopted in most clinical trials. This review briefly summarizes the potential synergistic anti-tumor effect and clinical development of the combination of anti-angiogenic agents and ICIs in NSCLC brain metastases, and discusses the existing challenges and problems

INTRODUCTION
POTENTIAL MECHANISMS
CLINICAL DATA
Pembrolizumab plus bevacizumab plus carboplatin plus paclitaxel
PREDICTIVE INDICATORS
Primary objective
DISCUSSION
Full Text
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