Ramucirumab: the long and winding road toward being an option for mCRC treatment

ABSTRACT

Introduction: Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality worldwide. Mortality is most often attributable to metastatic disease. Despite the progress achieved so far, life expectancy continues to be limited in most patients. Ramucirumab, a most recent antiangiogenic drug, is vying in the race to metastatic CRC (mCRC) treatment since its approval by the Food and Drug Administration (FDA), based on the results of the RAISE study.

Areas covered: This article reviews the role of ramucirumab in mCRC, including clinical indication, safety issues, and future perspectives.

Expert opinion: The use of Ramucirumab in clinical practice is still limited, probably due to economic burden and the lack of specific biomarkers. Future efforts will be addressed to improve our knowledge in the use of this drug and better guide us in patients’ care.

KEYWORDS:

• Metastatic colorectal cancer
• ramucirumab
• vascular endothelial growth factor inhibitor
• antiangiogenic agent
• biomarkers

Article highlights

• Ramucirumab is a fully human IgG1 MoAb that selectively binds VEGFR-2 and it is the most recently approved antiangiogenic drug for mCRC.

• Firstly, ramucirumab was approved for second-line treatment of gastric/gastroesophageal junction cancer either in monotherapy or in combination with paclitaxel. Subsequently, based on the results of RAISE trial, ramucirumab got FDA approval in combination with FOLFIRI for the second-line treatment of mCRC.

• The identification of potential biomarkers to drive the selection of the most appropriate antiangiogenic drugs is a compelling need. To date, translational research has been focused mostly on bevacizumab, but ramucirumab offers an appealing field of research.

• The landscape of antiangiogenic treatments in mCRC has broadened over the last few years, consequently the clinical algorithm is becoming more complex, but having several options could be of clear advantage to the patient and gives flexibility to the decision-making process.

• The typical and most frequent adverse event of ramucirumab include hypertension, proteinuria, impaired wound healing, gastrointestinal perforation, reversible posterior leukoencephalopathy syndrome, thromboembolic events, and bleeding.

• The use of ramucirumab in the treatment of mCRC in clinical practice is still limited, that is probably due to economic burden and complete lack of specific biomarkers, in light of this new studies are required and are ongoing to validate its role.

This box summarizes key points contained in the article.

Declaration of interest

Hans Prenen is a senior clinical investigator of the Belgian Foundation against Cancer. 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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The study is partially funded by Regione Veneto; grant RP-2014-00000395.