Analysis Of The Hla-I Genotypes In Patients With Solid Tumours Who Were Treated With Anti-Her Therapy

JOURNAL OF CLINICAL ONCOLOGY(2016)

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Abstract
e14505 Background: Better outcomes have been reported with the addition of Cetuximab and Trastuzumab to traditional chemotherapy schemes in colorectal, breast, head and neck cancer. Cetuximab (IgG1 chimeric monoclonal antibody whose specific target is the epidermal growth factor receptor EGFR) and Trastuzumab (Antibody G1 humanized monoclonal Ig that binds selectively to Her2 receptor) have an additional mechanism: antibody-mediated cytotoxicity (ADCC), showing that ADCC mediated by Trastuzumab and Cetuximab induces specific cellular immune response. This ADCC is mediated by NK cells. We try to analyse the different HLA genotypes in our series of metastatic cancer patient treated with these Mabs, and their impact on the evolution of the disease and the treatment efficacy. Methods: 116 patients from Reina Sofia University Hospital of Cordoba, treated with monoclonal antibody (Trastuzumab or Cetuximab) have been selected (55 colorectal, 39 breast and 22 head and neck) during the treatment. A sample of peripheral blood was collected; the extraction and purification of DNA, and performing HLA typing of class I alleles (HLA-BW4, HLA-BW6, HLA-C1, HLA-C2, HLA-C04) were performed. Clinical and histological treatment and evolution data of each patient were collected. This study was approved by the ethical committee of the Reina Sofia University Hospital (HURS). Results: In our study, patients who show HLA-B allele W4W4 have better time to treatment failure (TTF), median 16.06 months IC 95% (14.00-18.13), p = 0,019. A non-significant trend was observed in patients genotyped as HLA-C2C2 to have a worse TTF, 7.93 months IC 95% (6.10-9.75), compared to HLA C1C1 (P = 0.099). HLA C04 allele appears to be associated to worse TTF in breast cancer subgroup; 14.20 months IC 95% (3.43-24-69) p = 0.133. Conclusions: Different genotypes of HLA class I alleles could have been associated with time to treatment failure. Prospective studies are necessary to validate HLA alleles as biomarkers.
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Key words
solid tumours,genotypes,anti-her
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