Ramucirumab for the treatment of gastroesophageal cancers

Abstract

Introduction: In 2014, the US FDA-approved ramucirumab for use in the second-line setting of advanced or metastatic, gastric or gastroesophageal adenocarcinoma (GEAC) based on the result of Phase III clinical trials; REGARD and RAINBOW.

Areas covered: We briefly review the mechanisms of angiogenesis, antiangiogenic therapy and current status of advanced GEAC treatment then highlight the challenges and future prospects of novel molecular-targeted agents.

Expert opinion: Although both the REGARD and RAINBOW trials met their primary end points of significantly prolonged overall survival and progression-free survival, the magnitude of the difference is still relatively modest. Given that ramucirumab alone has a marginal effect, a combination of paclitaxel and ramucirumab is strongly preferred as a second-line therapy. To maximize the impact of ramucirumab in patients with GEAC, we can leverage the recent pharmacokinetics data of ramucirumab from the REGARD and RAINBOW trials. In addition, the quest for identifying biomarkers to select patients who are likely to benefit the most should continue. It is our firm belief that taxanes should no longer be added to the frontline regimens in most cases, given the success of the taxane/ramucirumab in the second-line setting.

Keywords:

• angiogenesis
• apatinib
• gastric adenocarcinoma
• gastroesophageal adenocarcinoma
• ramucirumab
• targeted therapy
• vascular endothelial growth factor
• VEGFR2

Acknowledgments

Generous grants from the Caporella, Dallas, Sultan, Park, Smith, Frazier, Oaks, Vanstekelenberg, Planjery, and Cantu Families. From the Schecter Private Foundation, Rivercreek Foundation, Kevin Fund, Myer Fund, Dio Fund, Milrod Fund, and Multidisciplinary Grants from the University of Texas M. D. Anderson Cancer Center, Houston, USA. Supported in part by the National Cancer Institute awardsCA138671, CA172741, CA129926 (JAA).

Declaration of interest

This paper was supported by National Cancer Institute awards CA138671, CA172741 and CA129926 to JA Ajani. In addition, JA Ajani has received honoraria, research funding and travel expenses as well as participated in a consultancy/advisory role for Lilly Oncology. 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.