FCGR2A and FCGR3A Polymorphisms Associated With Clinical Outcome of Epidermal Growth Factor Receptor–Expressing Metastatic Colorectal Cancer Patients Treated With Single-Agent Cetuximab

• DOI: 10.1200/jco.2006.08.8021
• Publication Date: 2007-08-17T22:23:29Z
• Authors: Wu Zhang; Michael Gordon; Anne M. Schultheis; Dong Yun Yang; Fumio Nagashima; Mizutomo Azuma; Heung-Moon Chang; Eva Borucka; Georg Lurje; Andy E. Sherrod; Syma Iqbal; Susan Groshen; Heinz-Josef Lenz
• Keywords: Progression-free survival

Purpose Cetuximab, a chimeric immunoglobulin G 1 (IgG1) anti–epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), has shown efficacy in 10% of patients with metastatic colorectal cancer (CRC). Recent studies demonstrate antibody-dependent cell-mediated cytotoxicity (ADCC) is one the modes action for rituximab and trastuzumab. Fragment c (Fc) portion IgG1 mAb to induce ADCC. gamma receptors (FcγR) play an important role initiating Studies have that two IgG FcγR polymorphisms (FCGR2A-H131R FCGR3A-V158F) independently predict response follicular lymphoma. We tested hypothesis whether these are associated clinical outcome CRC treated single-agent cetuximab. Patients Methods Thirty-nine were enrolled onto ImClone0144 trial. Using allele-specific polymerase chain reaction (PCR) –based method, gene FCGA2A-H131R FCGA3A-V158F assessed from genomic DNA extracted peripheral blood samples. Results FCGR2A-H131R FCGR3A-V158F progression-free survival (PFS; P = .037 .055, respectively; log-rank test). Combined analysis showed favorable genotypes (FCGR2A, any histidine allele, FCGR3A, phenylalanine allele) median PFS 3.7 months (95% CI, 2.4 4.4 months), whereas unfavorable (FCGR2A arginine/arginine or valine/valine) had 1.1 1.0 1.4 months; .004; Conclusion Our preliminary data suggest may be useful molecular markers cetuximab they indicate ADCC