Polymorphisms and Cetuximab Benefit in Locally Advanced Rectal Cancer

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Polymorphisms in FcγR (receptor for the constant region of immunoglobulin G) have been reported to be associated with improved immune-mediated effects of cetuximab (Erbitux) in metastatic colorectal cancer. In a study reported in Clinical Cancer Research, Sclafani and colleagues analyzed the association of FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms in peripheral blood samples with outcome in a subgroup of patients in the phase II EXPERT-C trial in patients with high-risk locally advanced rectal cancer; in this trial, patients received neoadjuvant CAPOX (capecitabine and oxaliplatin), chemoradiotherapy, and surgery followed by adjuvant CAPOX with or without cetuximab.

A total of 51 patients who received cetuximab and 50 who did not were included in the analysis. There was no association between the polymorphisms and tumor RAS status. Both FcγRIIa-131R (HR = 0.38, P = .058) and FcγRIIIa-158F alleles (HR = 0.21, P = .007) predicted improved progression-free survival in patients receiving cetuximab. Among cetuximab recipients, carriers of both 131R and 158F alleles vs those homozygous for either had a significant improvement in 5-year progression-free survival (78.4% vs 35.7%, HR = 0.22, P = .002) and 5-year overall survival (86.4% vs 57.1%, HR = 0.24, P = .018). The interaction between cetuximab benefit and 131R and 158F alleles was significant (P = .017) and remained so after adjustment for prognostic variables (P = .003).

The investigators concluded,  “This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in early stage colorectal cancer patients treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.” ■

Sclafani F, et al: Clin Cancer Res. July 1, 2014 (early release online).





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