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dc.contributor.authorLiu, Geoffrey-
dc.contributor.authorTu, Dongsheng-
dc.contributor.authorLewis, Marcia-
dc.contributor.authorCheng, Dangxiao-
dc.contributor.authorSullivan, Leslie A-
dc.contributor.authorChen, Zhuo-
dc.contributor.authorMorgen, Eric-
dc.contributor.authorSimes, John-
dc.contributor.authorPrice, Timothy J-
dc.contributor.authorTebbutt, Niall C-
dc.contributor.authorShapiro, Jeremy D-
dc.contributor.authorJeffery, G Mark-
dc.contributor.authorMellor, J Daniel-
dc.contributor.authorMikeska, Thomas-
dc.contributor.authorVirk, Shakeel-
dc.contributor.authorShepherd, Lois E-
dc.contributor.authorJonker, Derek J-
dc.contributor.authorO'Callaghan, Christopher J-
dc.contributor.authorZalcberg, John R-
dc.contributor.authorKarapetis, Christos S-
dc.contributor.authorDobrovic, Alexander-
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research 2016; 22(10): 2435-44-
dc.description.abstractTwo germline 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; both are reported to be associated with cetuximab-related outcomes. We performed a validation of these polymorphisms in NCIC CTG CO.17, a randomized trial of cetuximab monotherapy in refractory, metastatic colorectal cancer expressing EGFR. DNA extracted from formalin-fixed paraffin-embedded tissue was genotyped. In addition to log-rank tests, Cox proportional hazard models assessed their relationships with overall (OS) and progression-free survival (PFS), adjusting for clinically important prognostic factors, along with a polymorphism-treatment arm interaction term. Somatic KRAS status was wild-type for exon 2 in 153 (52%) of 293 patients, from whom tumor DNA was available. For FCGR2A H/H, a genotype-treatment interaction for KRAS wild-type patients was observed for OS (P = 0.03). In KRAS wild-type patients carrying FCGR2A H/H, cetuximab (vs. no cetuximab) improved survival substantially, with adjusted HRs (aHR) of 0.36 (OS) and 0.19 (PFS) and absolute benefits of 5.5 months (OS; P = 0.003) and 3.7 months (PFS; P = 0.02). In contrast, patients carrying FCGR2A R alleles (H/R or R/R) had aHRs of only 0.78 (OS; 2.8-month benefit) and 0.53 (PFS; 1.6-month benefit). No relationships were found for rs396991 (FCGR3A). In the CO.17 trial, cetuximab worked best for patients with KRAS wild-type colorectal cancers carrying FCGR2A H/H genotypes. Significantly lower benefits were observed in patients carrying germline FCGR2A R alleles. Clin Cancer Res; 22(10); 2435-44. ©2016 AACR.-
dc.titleFc-γ Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer.-
dc.typeClinical Trial, Phase III-
dc.typeJournal Article-
dc.typeMulticenter Study-
dc.typeRandomized Controlled Trial-
dc.identifier.journaltitleClinical cancer research : an official journal of the American Association for Cancer Research-
dc.identifier.affiliationPrincess Margaret Cancer Centre, Toronto, Canada-
dc.identifier.affiliationNCIC Clinical Trials Group and Queen's University, Kingston, Canada-
dc.identifier.affiliationTransgenomic, Inc., Omaha, Nebraska-
dc.identifier.affiliationUniversity of Sydney, Sydney, Australia-
dc.identifier.affiliationThe Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia-
dc.identifier.affiliationAustin Health, Heidelberg, Victoria, Australia-
dc.identifier.affiliationCabrini Hospital, Monash University, Melbourne, Australia-
dc.identifier.affiliationCanterbury Regional Cancer and Blood Service, Christchurch Hospital, Christchurch, New Zealand-
dc.identifier.affiliationPeter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia-
dc.identifier.affiliationTranslational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia-
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia-
dc.identifier.affiliationThe Ottawa Hospital, Ottawa, Canada-
dc.identifier.affiliationFlinders Centre for Innovation in Cancer, Flinders University, Adelaide, Australia-
Appears in Collections:Journal articles

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