Biomarker Indicates Which Patients With Colorectal Cancer Will Respond to Cetuximab

A blood-based test pinpoints which patients with metastatic colorectal cancer will benefit from treatment with cetuximab.1

Only approximately half of patients with incurable colorectal cancer benefit from cetuximab, and the reason behind its futility for so many patients has been a mystery.

"Our research discovered that the blood marker FCGR2A identifies a new group of patients that will benefit from taking cetuximab. With this finding, we believe we are now on the way to move it into the clinical setting to provide patients targeted, effective treatment," said Geoffrey Liu, MD, MSc, clinician-scientist at Princess Margaret Cancer Centre, University Health Network in Toronto, Ontario, Canada. The research was done in collaboration with the Canadian Cancer Trials Group and the Australasian Gastro-Intestinal Trials Group.

This study follows up on an international clinical trial published almost 10 years ago that found cetuximab improves overall survival and progression-free survival in patients with colorectal cancer in whom other treatments have failed.2

"In a group of metastatic colorectal cancer patients who were running out of treatment options, the previous clinical trial determined that cetuximab was most effective in a certain group of patients with tumors carrying a RAS mutation,” said Liu. “But it certainly didn't work for everyone and so the race was on to find out how to better identify which patients would benefit from this drug."

Liu explained that their finding came from analyzing archived tumor and normal tissue samples from 527 of the patients who were enrolled in the earlier trial. They analyzed blood and normal tissues for heritable genetic variations.

Cetuximab was found to work best for patients whose colorectal cancer had the wild-type version of the KRAS gene and the FCGR2A H/H genotypes. Cetuximab was significantly less beneficial for patients with germline, or inherited, FCGR2A R alleles.

Reference

1. Liu G, Tu D, Lewis M, et al. Fc-γ receptor polymorphisms, cetuximab therapy, and survival in the NCIC CTG CO.17 trial of colorectal cancer [published online ahead of print May 15, 2016]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-15-0414.

2. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. New Engl J Med. 2007;357(20):2040-2048.

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