EGFR-targeting monoclonal antibodies found to increase risk of fatal adverse events

This meta-analysis examined the risk of fatal adverse events among various advanced cancer patients receiving EGFR-targeting monoclonal antibodies.

A mutation causing the overproduction (termed overexpression) of epidermal growth factor receptor (EGFR), which plays a role in the creation, migration, and survival of cancer cells, has been implicated in the development of various tumors, including colorectal cancer. Blocking the effects of EGFR has been the focus of cancer research for several years. Two types of EGFR-targeting agents currently approved for the treatment of advanced cancer patients are monoclonal antibodies, including cetuximab (Erbitux) and panitumumab (Vectibix), and small-molecule tyrosine kinase inhibitors, such as gefitinib (Iressa) and erlotinib (Tarceva). While the risk of fatal adverse events, or death caused by the treatment, was found to be relatively low with the use of tyrosine kinase inhibitors, the risk associated with monoclonal antibodies is less understood. The current meta-analysis (an analysis of data combined from several similar studies) examined the safety of monoclonal antibodies used in the treatment of solid tumors, including colorectal cancer patients.

This analysis examined 21 studies including a total of 14,766 patients. Eleven of these studies focused on colorectal cancer, while the remaining studies also included patients with lung, pancreatic, and breast cancer.

Pooling the results of all 21 studies, the overall rate of fatal adverse events among patients receiving either cetuximab or panitumumab was 1.7%. Specifically among colorectal cancer patients, the incidence of fatal adverse events among patients receiving monoclonal antibodies was 1.6%. The use of monoclonal antibodies was found to increase the odds of a fatal adverse event by more than 30% compared to patients receiving other forms of therapy. When examining the use of different monoclonal antibodies separately, the rate of fatal adverse events with cetuximab was higher than that seen with panitumumab (2.0% versus 0.9%). Results indicate that there is no significant association between the duration of treatment with monoclonal antibodies and the risk of fatal adverse events.

This analysis concluded that the use of EGFR-targeting monoclonal antibodies increases the risk of fatal adverse events among advanced cancer patients.

Despite these findings, both cetuximab and panitumumab have been shown to benefit cancer patients matching treatment indications. Patients and physicians should be aware of the risks associated with monoclonal antibody use and strategies to reduce adverse events should be investigated. In addition, the conclusions of this study are contradicted by a recent meta-analysis which concluded cetuximab is associated with only a non-significant increase in the risk of fatal adverse events among colorectal cancer patients. Although in comparison, the current study included a much larger number of trials and patients analyzed.

Consult with your physician regarding the risks and benefits of EGFR-targeting monoclonal antibodies in the treatment of colorectal cancer.