The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer

Abstract

Angiogenesis is one of the most important phenomena sustaining tumor development and metastatization, including for non small cell lung cancer (NSCLC). A dominant role in angiogenesis is played by the vascular endothelial growth factor (VEGF) and its signaling pathway. Ramucirumab, is a fully human immunoglobulin G1 monoclonal antibody that binds to the extracellular domain of the VEGF receptor-2 (VEGFR-2) with high specificity and affinity blocking the interaction of VEGFR-2 and VEGF ligands, thus inhibiting their signaling pathways and the consequential endothelial proliferation and migration. A recent phase III randomized trial named REVEL, demonstrated the efficacy of ramucirumab in combination with docetaxel as second line treatment of advanced NSCLC, leading to its FDA and EMA approval in this clinical setting. In the REVEL trial advanced NSCLC patients whose disease had progressed after first line platinum-based chemotherapy, were administered ramucirumab plus docetaxel or placebo plus docetaxel. More than 1,250 patients were treated and patients randomized to the treatment with ramucirumab plus docetaxel showed a significant longer median overall survival compared to those randomized to chemotherapy only. Ramucirumab is the first antiangiogenetic agent approved in the treatment both of squamous and non squamous NSCLC. In fact, it is not associated with increased risk of respiratory bleeding in the squamous histology, and also has demonstrated efficacy in both histology types. The role of ramucirumab, already cleared in the second-line treatment of advanced NSCLC, needs to be clarified further and is currently being explored also in the first-line treatment of advanced NSCLC.

Keywords: Angiogenesis; VEGF; VEGFR2; advanced NSCLC; ramucirumab; second-line treatment.