Ramucirumab as second-line treatment for patients with metastatic esophagogastric adenocarcinoma

Abstract

Ramucirumab is a fully humanized monoclonal antibody targeting the extracellular domain of the VEGF receptor 2. It prevents ligand binding to VEGF receptor 2 and receptor-mediated pathway activation in endothelial cells. After promising Phase I trial results in a variety of tumor types, two pivotal placebo-controlled Phase III trials conducted in patients with pretreated metastatic esophagogastric adenocarcinoma demonstrated significant clinical activity regarding the prolongation of overall survival both as monotherapy (REGARD study) and in combination with paclitaxel (RAINBOW study). Currently, ramucirumab is being investigated in the first-line treatment of esophagogastric adenocarcinoma in combination with capecitabine and cisplatin in a Phase III trial (RAINFALL).

Keywords:

• anti-angiogenic treatment
• gastroesophageal cancer
• paclitaxel
• ramucirumab
• second-line therapy

Financial & competing interests disclosure

The authors received honoraria for lectures from Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Ramucirumab is a fully humanized immunoglobulin G1 monoclonal antibody targeting the extracellular domain 3 of the VEGF receptor 2.

• Significant preliminary anti-tumor activity in several tumor types has been observed in a large Phase I trial, while ramucirumab was well tolerated without new safety findings compared with established anti-angiogenic drugs.

• Two pivotal studies in patients with pretreated esophagogastric adenocarcinoma have reached their end point of prolonging overall survival with ramucirumab both as monotherapy when tested against placebo and in combination with paclitaxel versus paclitaxel/placebo.

• Consequently, ramucirumab has been granted approval by the US FDA and European Medicines Association in 2014 for the first-line treatment of esophagogastric adenocarcinoma.

• A first-line trial investigating the addition of ramucirumab to capecitabine/cisplatin has been initiated.