التفاصيل البيبلوغرافية
| العنوان: |
Data from Fc-γ Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer |
| المؤلفون: |
Alexander Dobrovic, Christos S. Karapetis, John R. Zalcberg, Christopher J. O'Callaghan, Derek J. Jonker, Lois E. Shepherd, Shakeel Virk, Thomas Mikeska, J. Daniel Mellor, G. Mark Jeffery, Jeremy D. Shapiro, Niall C. Tebbutt, Timothy J. Price, John Simes, Eric Morgen, Zhuo Chen, Leslie A. Sullivan, Dangxiao Cheng, Marcia Lewis, Dongsheng Tu, Geoffrey Liu |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
Purpose: Two 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.Experimental Design: 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.Results: 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).Conclusions: 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. |
| DOI: |
10.1158/1078-0432.c.6523949 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a37513384d82189607b871a3b393e969
https://doi.org/10.1158/1078-0432.c.6523949 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....a37513384d82189607b871a3b393e969 |
| قاعدة البيانات: |
OpenAIRE |