The Role of the Antiangiogenetic Ramucirumab in the Treatment of Advanced Non Small Cell Lung Cancer
2017
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.
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