(ChemotherapyAdvisor) – Among patients with metastatic colorectal cancer (mCRC), Fragment c gamma receptor (FcGR) polymorphisms predict progression-free survival (PFS) following second-line treatment with cetuximab and FOLFIRI, and may prove to be a useful biomarker for selecting patients for cetuximab therapy, according to a study presented at the European Society for Medical Oncology (ESMO) annual meeting in Vienna, Austria.
“Our data suggest that the FcGR3a polymorphisms may be useful molecular markers to predict clinical outcome in mCRC patients treated with cetuximab,” reported Y. Inoue and coauthors, of the Yamaguchi University School of Medicine in Ube, Japan.
Recent studies suggest that antibody-dependent cell-mediated cytotoxicity is one mode of action for cetuximab. FcGR play an important role in initiating ADCC, the authors noted.
The team studied associations between FcGR polymorphisms and clinical outcomes among patients with KRAS-wild type mCRC, following second-line cetuximab + FOLFIRI treatment.
Tumor tissues from 56 patients with wild-type KRAS tumor status were sequenced and genotyped for BRAF and P13K mutations and FcGR2a (H131R) and FcGR3a (V158F) polymorphisms. Associations between each FcGR polymorphism and response rate (RR) and PFS were then analyzed.
No patient with BRAF or PI3K mutations was responsive to the regimen, the authors reported.
“A statistically significant difference was observed for PFS for F carriers (compared) to 158V/V patients (286 vs 154 days; P = 0.047),” the authors reported. The difference was more significant among F-carriers with no BRAF or PI3K mutations (301 vs 185 days; P = 0.016).
RR among all 56 patients was 33.9%. There were no significant associations between each polymorphism and RR, the authors reported.
“Super-responding” patients might be selected for cetuximab therapy using a combination of FcGR3a and BRAF and PI3K mutations, they suggested.
ESMO Abstract (#237)