@article{109029b31e1342dca7b178cd0763cb9f,
title = "Fc-gamma receptor polymorphisms, cetuximab therapy, and overall survival in the CCTG CO.20 trial of metastatic colorectal cancer",
abstract = "Background: Two germ line Fc-γ receptor (FCGR) polymorphisms, rs1801274 [FCGR2A; His(H)131Arg(R)] and rs396991 [FCGR3A; Phe(F)158Val(V)], produce altered proteins through amino acid substitutions. We previously reported that the FCGR2A H/H genotype was associated with longer overall survival (OS) in cetuximab-treated chemotherapy-refractory patients with metastatic colorectal cancer. Here, we aimed to replicate and extend this finding in the Canadian Clinical Trials Group CO.20 trial. Methods: After germ line DNA genotyping, polymorphic relationships with survival were assessed using log-rank tests and hazard ratios (HR) from Cox proportional hazard models, adjusting for known prognostic factors. The dominant genetic inheritance model was used for the main analysis. Results: Of 592 wild-type KRAS patients treated with cetuximab, those with the FCGR2A H/H genotype (n = 165, 28%) had improved OS (HR: 0.66, P < 0.001; median absolute benefit, 1.3 months) compared to those with R/- genotype (n = 427, 72%). Patients with H/R had intermediate results under a codominant genetic inheritance model (HR: 0.72, P = 0.003). No significant associations were found between FCGR3A genotype and OS. In an exploratory analysis, patients with the combination of FCGR2A H/H + FCGR3A F/F genotype had significantly better OS (HR: 0.33, P = 0.003; median absolute benefit, 12.5 months) than patients with the combination of double-variant R/R + V/V genotype. Progression-free survival results were similar to OS. Toxicity rates were not associated with either polymorphism. Conclusions: The FCGR2A genotype was associated with efficacy but not with toxicity in wild-type KRAS, cetuximab-treated colorectal cancer patients. FCGR3A genotype may modulate the relationship between FCGR2A polymorphism and outcome. FCGR2A is a promising biomarker for clinical management for these patients.",
keywords = "FCGR2A, FCGR3A, cetuximab, polymorphism, survival",
author = "Daniel Shepshelovich and Townsend, {Amanda R.} and Osvaldo Espin-Garcia and Lidija Latifovic and O{\textquoteright}Callaghan, {Chris J.} and Jonker, {Derek J.} and Dongsheng Tu and Eric Chen and Eric Morgen and Price, {Timothy J.} and Jeremy Shapiro and Siu, {Lillian L.} and Michiaki Kubo and Alexander Dobrovic and Ratain, {Mark J.} and Wei Xu and Taisei Mushiroda and Geoffrey Liu",
note = "Publisher Copyright: {\textcopyright} 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2018",
month = nov,
doi = "10.1002/cam4.1819",
language = "אנגלית",
volume = "7",
pages = "5478--5487",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Inc.",
number = "11",
}