Phase 2 Trial of Bevacizumab in Combination With Pemetrexed

Brain metastases are a common complication of advanced non-small-cell lung cancer (NSCLC) both at initial presentation and at the time of disease progression. Patients with brain metastases have often been excluded from large randomized phase III trials due to concerns of poorer survival and impaired ability of drugs to cross the blood-brain barrier. However, as survival has improved, some trials have included such patients, often finding similar benefit to patients with metastatic disease elsewhere. Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor, has emerged as an important adjunct to platinum-based chemotherapy doublets for use in advanced NSCLC. This drug is normally used as a first line chemotherapy. Pemetrexed is a multi-targeted anti-folate agent,which is approved for use in first-line (with platinum), maintenance, and second-line treatment of advanced nonsquamous NSCLC. Based on the efficacy of pemetrexed as a second line agent and the safety questions surrounding bevacizumab in those with treated brain metastases, a trial was designed to look at the combination of both agents as a second line therapy in NSCLC patients with treated stable brain metastases