Patients with the H/H genotype in the FCGR2A gene have higher survival rates when treated with cetuximab than do patients with the H/R and R/R genotypes, investigators reported.
In addition, polymorphism in the FCGR3A gene had no effect on survival.
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“Only a proportion of patients with colorectal cancer receiving cetuximab derive benefit from the drug. However, other than RAS and BRAF mutations, no biomarkers have been identified as clinically useful predictors of response to cetuximab. Our primary objective was to determine whether survival is affected by a significant interaction between FCGR polymorphism and cetuximab treatment after adjusting for other potential prognostic factors,” wrote Dr. Geoffrey Liu of the University of Toronto and his associates (Clin Cancer Res. 2016 May 15;22:2435-44).
Cetuximab is a therapeutic monoclonal antibody that inhibits epidermal growth factor receptors by binding to their extracellular domain. Cetuximab also induces antibody-dependent cell cytotoxicity and promotes the endocytic and phagocytic activity in immune cells by binding to the Fc-gamma receptor (FCGR) of host effector cells. FCGR has a genetic polymorphism in the coding region of the FCGR2A gene that causes an amino acid change from histidine (H) to arginine (R). FCGR also has a genetic polymorphism in the coding region of the FCGR3A gene that causes an amino acid change from phenylalinine (F) to valine (V).
Dr. Liu and associates collected patient demographic information and clinical outcome data (overall survival and progression-free survival) from the NCIC CTG CO.17 database and tumor tissue samples from the NCIC CTG central tumor bank. DNA was genotyped blindly. From an original cohort of 572 patients with colorectal cancer, 286 patients had usable FCGR2A genetic data, and 288 patients had usable FCGR3A genetic data. Genetic polymorphisms were not associated with age, sex, performance status, disease site, prior therapies, and site/number of metastatic sites.
In Cox proportional hazard models controlling for clinically relevant factors, patients with the H/H genotype (HR, 7.95; 95% CI, 5.2-10.6) had greater survival benefits than patients with the H/R (HR, 6.6; 95% CI, 5.0-9.1) or R/R (HR, 6.34; 95% CI, 4.5-9.1) genotypes when treated with cetuximab (P = .01). There were no significant relationships between overall or progression-free survival and FCGR3A polymorphisms.
“This prognostic observation should be replicated in other colorectal cancer populations and possibly in other cancers, such as breast cancer or lymphoma, before being generalized into other settings,” the investigators wrote.
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