Ramucirumab as Second-Line Systemic Therapy in Hepatocellular Carcinoma

Ramucirumab, a molecular targeted agent, is a recombinant human IgG1 monoclonal antibody directed against vascular endothelial growth factor receptor 2 (VEGFR-2) that plays an important role in vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. It inhibits VEGFR-2 activation by blocking its binding to VEGF-A, VEGF-C, and VEGF-D, thereby inhibiting endothelial growth, migration, and survival and exerting antitumor effects via inhibition of tumor angiogenesis. Ramucirumab is currently indicated for unresectable advanced/recurrent gastric cancer, colorectal cancer, and non-small-cell lung cancer and is used in routine clinical practice. A randomized phase III trial (REACH-2) investigated ramucirumab as second-line treatment following first-line sorafenib therapy for advanced hepatocellular carcinoma (HCC) in patients with an alpha-fetoprotein (AFP) level ≥400 ng/mL, and results demonstrating the superiority of ramucirumab over placebo in overall survival (OS) were reported at the American Society of Clinical Oncology (ASCO) annual meeting in June 2018. This article outlines the results of the REACH-2 trial and previous clinical trials of ramucirumab (REACH).