An evidence-based review of the incidence of CNS bleeding with anti-VEGF therapy in non-small cell lung cancer patients with brain metastases

Background: Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis. Solid tumors, including non-small cell lung cancer (NSCLC), are dependent on angiogenesis for growth and metastasis. Anti-VEGF therapy has demonstrated clinical benefits in the first-line treatment of NSCLC. Central nervous system (CNS) metastases are a common occurrence among patients with lung cancer and confer significant morbidity and mortality. The risk of CNS hemorrhage in NSCLC patients receiving anti-VEGF therapy is still relatively unexplored because patients with CNS metastases have generally been excluded from trials of anti-VEGF therapy due to a perceived increased risk of cerebral hemorrhage. Recently, large prospective, randomized trials, open-label studies and observational cohort studies in NSCLC have provided data on the incidence of CNS hemorrhage in large patient populations, reflective of community practice. Methods: We conducted a literature review for the available data on the incidence of CNS hemorrhage in NSCLC patients with brain metastases receiving anti-VEGF therapy. Results: There is no significantly increased risk of CNS hemorrhage in patients with NSCLC and emerging (previously untreated) or pretreated CNS metastases receiving anti-VEGF therapy. Conclusions: We conclude that clinical trial data indicate that anti-VEGF therapy can be considered for NSCLC patients with emerging or pretreated CNS metastases. (C) 2012 Published by Elsevier Ireland Ltd.