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FcγRIIa and FcγRIIIa polymorphisms and cetuximab benefit in the microscopic disease.
Sclafani, Francesco; Gonzalez de Castro, David; Cunningham, David; Hulkki Wilson, Sanna; Peckitt, Clare; Capdevila, Jaume; Glimelius, Bengt; Roselló Keränen, Susana; Wotherspoon, Andrew; Brown, Gina; Tait, Diana; Begum, Ruwaida; Thomas, Janet; Oates, Jacqueline; Chau, Ian.
Afiliação
  • Sclafani F; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Gonzalez de Castro D; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Cunningham D; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom. david.cunningham@rmh.nhs.uk.
  • Hulkki Wilson S; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Peckitt C; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Capdevila J; Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Glimelius B; Akademiska Sjukhuset Uppsala, Uppsala, Sweden.
  • Roselló Keränen S; Institute of Health Research Hospital Clinic of Valencia, University of Valencia, Valencia, Spain.
  • Wotherspoon A; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Brown G; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Tait D; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Begum R; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Thomas J; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Oates J; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
  • Chau I; The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom.
Clin Cancer Res ; 20(17): 4511-9, 2014 Sep 01.
Article em En | MEDLINE | ID: mdl-24987061
PURPOSE: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX±cetuximab in high-risk, locally advanced rectal cancer. EXPERIMENTAL DESIGN: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan-Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. RESULTS: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX=54, CAPOX-C=51). No deviation from the Hardy-Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. FcγRIIa-131R (HR, 0.38; P=0.058) and FcγRIIIa-158F alleles (HR, 0.21; P=0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P=0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P=0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P=0.017) and remained significant after adjusting for prognostic variables (P=0.003). CONCLUSION: This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article