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Fc gamma RIIa and F...
Fc gamma RIIa and Fc gamma RIIIa Polymorphisms and Cetuximab Benefit in the Microscopic Disease
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Sclafani, Francesco (author)
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de Castro, David Gonzalez (author)
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Cunningham, David (author)
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Wilson, Sanna Hulkki (author)
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Peckitt, Clare (author)
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Capdevila, Jaume (author)
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- Glimelius, Bengt (author)
- Uppsala universitet,Enheten för onkologi
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Keraenen, Susana Rosello (author)
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Wotherspoon, Andrew (author)
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Brown, Gina (author)
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Tait, Diana (author)
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Begum, Ruwaida (author)
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Thomas, Janet (author)
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Oates, Jacqueline (author)
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Chau, Ian (author)
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(creator_code:org_t)
- 2014
- 2014
- English.
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 20:17, s. 4511-4519
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Purpose: Fc gamma R 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: Fc gamma RIIa-H131R and Fc gamma RIIIa-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 fromthe Hardy-Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. Fc gamma RIIa-131R (HR, 0.38; P = 0.058) and Fc gamma RIIIa-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 Fc gamma RIIa and Fc gamma RIIIa 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Sclafani, France ...
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de Castro, David ...
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Cunningham, Davi ...
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Wilson, Sanna Hu ...
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Peckitt, Clare
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Capdevila, Jaume
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show more...
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Glimelius, Bengt
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Keraenen, Susana ...
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Wotherspoon, And ...
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Brown, Gina
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Tait, Diana
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Begum, Ruwaida
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Thomas, Janet
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Oates, Jacquelin ...
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Chau, Ian
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Clinical Cancer ...
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Uppsala University