The coming of ramucirumab in the landscape of anti-angiogenic drugs: potential clinical and translational perspectives

Abstract

Introduction: Angiogenesis plays a pivotal role in the development and progression of tumors and it represents a crucial target for therapeutic strategies. Until now, regulatory agencies approved antiangiogenic agents targeting the VEGF and multi-target agents carrying antiangiogenic and anti-proliferative effects. They often provide only a modest survival benefit and their role in clinical practice is debated. The limited efficacy may be partially explained by the complexity of the molecular background of angiogenic processes, composed of several pathways interacting with both tumor cells and the microenvironment.

Areas covered: Ramucirumab is a fully human monoclonal antibody selectively binding and inhibiting the VEGF receptor 2 (VEGFR-2), a crucial molecule involved in angiogenesis. A series of Phase I–II trials conducted in a wide spectrum of malignancies reported promising antitumor activity. In 2014, data from large Phase III clinical trials in gastrointestinal, lung and breast malignancies were released.

Expert opinion: Considering the evidences of efficacy emerging from the available Phase III trials, the antiangiogenic approach emerged as a promising strategy particularly for the treatment of gastric cancer. Nevertheless, the identification and validation of potentially predictive biomarkers are necessary to improve the selection of patients and the globally awaited clinical benefit.

Keywords:

• angiogenesis
• gastric cancer
• ramucirumab
• review

Acknowledgments

This work was partially supported by a grant of the Italian Association for Cancer Research (AIRC-MFAG 14282) and a fellowship award of the International Association for the Study of Lung Cancer (IASLC). L Calvetti and S Pilotto share the first co-authorship; G Tortora and E Bria share the last co-authorship.

Declaration of interest

E Bria is a consultant for Celgene, participates on advisory boards for Novartis, Astra-Zeneca, and Pierre-Fabre and receives speaker fees from Pfizer. G Tortora is a consultant for Novartis, Pfizer, and GlaxoSmithKline. This work was partially supported by a grant of the Italian Association for Cancer Research (AIRC-MFAG 14282) and a fellowship award of the International Association for Lung Cancer (IASLC). 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.