The safety of monoclonal antibodies for treatment of colorectal cancer

ABSTRACT

Introduction: Monoclonal antibodies such as bevacizumab, ramucirumab, cetuximab and panitumumab play an important role in the treatment of metastatic colorectal cancer (mCRC). With the introduction of these drugs considerable improvements in both progression-free survival (PFS) and overall survival (OS) were achieved. However these antibodies are associated with a unique side effect profile.

Areas covered: This review provides an overview about drug efficacy of bevacizumab, cetuximab, panitumumab and ramucirumab in the treatment algorithm of mCRC. Additionally, we discuss the most common toxicites of these monoclonal antibodies.

Expert opinion: The most common toxicities associated with the VEGF-A directed antibody bevacizumab are hypertension, proteinuria, thromboembolism, bleeding, gastrointestinal perforation and prolonged wound healing. Similarly, the rate of hypertension and proteinuria is increased during treatment with the VEGFR2 antibody ramucirumab.

On the other hand the most frequent side effects of EGFR targeted antibodies are skin rash, hypersensitivity reactions and hypomagnesemia. Due to the murine portions of cetuximab the incidence of infusion reactions is more frequent compared to panitumumab which is a pure human monoclonal antibody.

KEYWORDS:

• Colorectal cancer
• drug safety
• monoclonal antibodies
• bevacizumab
• ramucirumab
• cetuximab
• panitumumab

Article highlights

• The introduction of monoclonal antibodies resulted in improved outcomes for mCRC patients.

• Monoclonal antibodies have a unique side-effect profile.

• The most common side effects of bevacizumab are hypertension, proteinuria, thromboembolism, bleeding, GIP, and prolonged wound healing.

• Especially, the rate of hypertension and proteinuria is increased during treatment with ramucirumab.

• Typical side effects of cetuximab are skin rash, infusion reactions, and hypomagnesemia.

• Occurrence of skin rash predicts a good response to anti-EGFR therapy.

• Contrary to cetuximab, which is a chimeric antibody (human/mouse), panitumumab is a fully human monoclonal antibody and, therefore, has a lower immunogenic potential resulting in markedly less infusion reaction (<1%).

This box summarizes key points contained in the article.

Declaration of interest

MD Berger was supported by a grant from the Swiss Cancer League (BIL KLS-3334-02-2014) and by a grant from the Werner and Hedy Berger-Janser Foundation for cancer research. HJ Lenz received financial support from the Gloria Borges Wunderglo Project. HJ Lenz has also received support from Merck Serono, Roche and Bayer. 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.