Optimizing the dose and schedule of anti-vascular endothelial growth factor antibodies in non-small-cell lung cancer

Abstract

Lung cancer is the world's leading cause of cancer death. Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease. Median survival is approximately 8-10 months for patients who receive standard platinum-based doublet therapy. In 2006 the FDA approved the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab for patients with advanced, non-squamous, NSCLC based on the Eastern Cooperative Oncology Group E4599 trial. This trial demonstrated a 2-month improvement in overall survival when bevacizumab was added to carboplatin/paclitaxel. European investigators presented further data supporting improvement in progression-free survival with the use of bevacizumab and a cisplatin doublet in the Avastin in Lung Cancer (AVAiL) trial. Bevacizumab at doses of 7.5 mg/kg and 15 mg/kg are both effective and safe for patients with advanced NSCLC. Fatal hemorrhage has been reported for patients receiving the antiangiogenesis antibody. According to a retrospective study, the only significant clinical and radiographic variable associated with increased risk of pulmonary hemorrhage is the presence of cavitation. Common side effects include hypertension, proteinuria and minor mucosal bleeding. Bevacizumab monotherapy given every 21 days can be safely continued for patients without evidence of progression and for whom side effects of therapy are acceptable. Many questions remain, such as the role of the anti-VEGF antibody in early-stage disease, the safety of bevacizumab in patients with squamous histology NSCLC, and the benefit of combination therapy in elderly patients.