Sistema de Salut de Catalunya
Institut Català de la Salut
[Borrero-Palacios A, Cebrián A, Gómez Del Pulgar MT] Translational Oncology Division, Oncohealth Institute, Hospital Universitario "Fundación Jimenez Diaz", Madrid, Spain. [García-Carbonero R] Medical Oncology Department, Hospital Virgen del Rocío, Sevilla, Spain. [García P] Medical Oncology Department, Hospital Gral. Univ. Gregorio Marañón, Madrid, Spain. [Aranda E] Medical Oncology Department, Hospital Universitario Reina Sofía, Córdoba, Spain. [Elez E] Servei d’Oncologia Mèdica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Vall d'Hebron Barcelona Hospital Campus
2019-04-01T07:17:42Z
2019-04-01T07:17:42Z
2019-02-22
Cetuximab; Metastatic colorectal cancer; KIR genes
Cetuximab; Càncer colorectal amb metàstasi; Gens KIR
Cetuximab; Cáncer colorrectal con metástasis; Genes KIR
Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08-4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.
Article
Published version
English
Còlon - Càncer; Mutació (Biologia); Cetuximab; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized::Cetuximab; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Natural Killer Cell::Receptors, KIR; Other subheadings::Other subheadings::Other subheadings::/genetics; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados::cetuximab; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores de células asesinas naturales::receptores KIR; Otros calificadores::Otros calificadores::Otros calificadores::/genética
Nature Research
Scientific Reports;9(1)
https://www.nature.com/articles/s41598-019-39291-2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
Articles científics - HVH [3440]
