Genetic Polymorphisms of <i>Fc</i>γ<i>RIIa</i> and<i> Fc</i>γ<i>RIIIa</i> Are Not Predictive of Clinical Outcomes after Cetuximab plus Irinotecan Chemotherapy in Patients with Metastatic Colorectal Cancer

Abstract

<i>Objective:</i> The anti-epidermal growth factor receptor monoclonal antibody cetuximab has been shown to be effective in patients with wild-type<i> KRAS</i> metastatic colorectal cancer (mCRC). Fragment C γ receptor <i>(Fc</i>γ<i>R)</i> polymorphisms may predict the effectiveness of cetuximab, but this has not been established. This study investigated the clinical relevance of <i>Fc</i>γ<i>R</i> gene polymorphisms and <i>KRAS</i> status in iri-notecan-refractory mCRC patients treated with cetuximab. <i>Methods:</i> The total number of irinotecan-refractory mCRC patients studied was 118. Among them, 117 and 107 patients were screened for <i>KRAS</i> mutations and genetic polymorphisms of <i>Fc</i>γ<i>RIIa-131H/R</i> and <i>Fc</i>γ<i>RIIIa-158V/F</i>, respectively. The association of <i>Fc</i>γ<i>R </i>polymorphisms and<i> KRAS </i>mutations with clinical outcome was analyzed. <i>Results:</i><i>KRAS</i> mutations were found in 33 patients (27.1%). Wild-type <i>KRAS</i> was associated with a better response rate (p < 0.001), longer progression-free survival (p < 0.001) and longer overall survival (p < 0.001). <i>Fc</i>γ<i>RIIa H/H, H/R </i>and<i> R/R </i>polymorphisms were observed in 54, 49 and 4 patients, respectively, and <i>Fc</i>γ<i>RIIIa V/V, V/F </i>and <i>F/F </i>polymorphisms were observed in 6, 65, and 36 patients, respectively. Clinical outcomes were not significantly associated with either <i>Fc</i>γ<i>RIIa</i> or <i>Fc</i>γ<i>RIIIa</i> polymorphisms or with combinations of <i>KRAS </i>status and <i>Fc</i>γ<i>R </i>polymorphisms. <i>Conclusion:</i> The <i>Fc</i>γ<i>RIIa</i> and <i>Fc</i>γ<i>RIIIa</i> polymorphisms may not be useful molecular biomarkers for the activity of cetuximab in patients with mCRC.