Anti-angiogenetic therapies for central nervous system metastases from non-small cell lung cancer

Abstract

Central nervous system (CNS) metastases are common in patients with advanced non-small cell lung cancer (NSCLC), occurring in 24% to 44% of patients in the course of their disease and confer significant morbidity and mortality. Systemic therapies have been deemed ineffective in brain metastases (BM) under the hypothesis that the blood-brain barrier (BBB) limits their delivery to the brain. Angiogenesis, which is mainly mediated by vascular endothelial growth factor (VEGF) pathway, is crucial for tumor survival, growth and invasion both in primary and metastatic brain lesions. Two major categories of agents have been developed to target this pathway: antibody-based agents and VEGF receptor tyrosine kinase inhibitors (TKIs). Clinical benefits have been shown with anti-angiogenetic therapies in the treatment of metastatic NSCLC. However, patients with CNS metastases were often excluded from trials with these agents, due to concerns about a potentially greater risk of cerebral haemorrhage and thromboembolic disease. Therefore, the overall efficacy and safety of angiogenetic agents in patients with BM from NSCLC are yet to be clarified. This paper aims to review available data about the efficacy and safety of antiangiogenetic therapies for CNS metastases in NSCLC patients.

Potential benefit of osimertinib plus bevacizumab in leptomeningeal metastasis with EGFR mutant non-small-cell lung cancer

“…Tumor vascularization is critical to the pathogenesis of solid tumors, and TMD is related to tumor invasiveness and metastasis formation which could be used as a potential predictive marker for bevacizumab benefit [ 38 ]. This antagonistic effect of VEGF inhibit immature angiogenesis and induce vascular normalization, thus increasing the internal perfusion of the tumor and increasing the rate of drug delivery [ 39 ]. In theory, bevacizumab increases the rate of drug entry into the brain, combined with osimertinib possibly have more advantageous in the control of intracranial lesions.…”

Intrathecal chemotherapy combined with systemic therapy in patients with refractory leptomeningeal metastasis of non-small cell lung cancer: a retrospective study

“…Both univariate and multivariate analyses showed that the use of bevacizumab was a good prognostic factor for NSCLC LM patients with combination therapy. Bevacizumab is a recombinant humanized IgG1 monoclonal antibody against vascular endothelial growth factor (VEGF), which specifically binds to VEGF to block its binding to its receptor, thus reducing angiogenesis, inducing the degeneration of existing blood vessels, inhibiting tumour formation, inhibiting immature angiogenesis, and inducing vascular normalization [ 24 ]. Animal studies have shown that antiangiogenic treatment can prolong the survival time of LM mice [ 25 ].…”

Apatinib Monotherapy or Combination Therapy for Non-Small Cell Lung Cancer Patients With Brain Metastases

“…In this study, apatinib was well tolerated in all patients, and no grade 3/4 AEs were observed. Cerebral hemorrhage is one of the most common side effects in patients who receive antivascular therapies 36,37 . However, no cerebral hemorrhage and no other severe AEs were documented in all enrolled patients.…”