Publicaciones científicas
Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer
Borrero-Palacios A (1), Cebrián A (2), Gómez Del Pulgar MT (1), García-Carbonero R (3), García P (4), Aranda E (5), Elez E (6), López-López R (7), Cervantes A (8), Valladares M (9), Nadal C (10), Viéitez JM (11), Guillén-Ponce C (12), Rodríguez J (13), Hernández I (14), García JL (15), Vega-Bravo R (16), Puime-Otin A (16), Martínez-Useros J (1), Del Puerto-Nevado L (1), Rincón R (1), Rodríguez-Remírez M (1), Rojo F (16), García-Foncillas J (17).
(1) Translational Oncology Division, Oncohealth Institute, Hospital Universitario "Fundación Jimenez Diaz", Madrid, Spain.
(2) Translational Oncology Division, Oncohealth Institute, Hospital Universitario "Fundación Jimenez Diaz", Madrid, Spain.
(3) Medical Oncology Department, Hospital Virgen del Rocío, Sevilla, Spain.
(4) Medical Oncology Department, Hospital Gral. Univ. Gregorio Marañón, Madrid, Spain.
(5) Medical Oncology Department, Hospital Universitario Reina Sofía, Córdoba, Spain.
(6) Medical Oncology Department, Hospital Vall d'Hebrón, Barcelona, Spain.
(7) Medical Oncology Department, Complexo Hospitalario Universitario Santiago de Compostela, Galicia, Spain.
(8) Medical Oncology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain.
(9) Medical Oncology Department, Complejo Hospitalario Universitario A Coruña, Galicia, Spain.
(10) Medical Oncology Department, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain.
(11) Medical Oncology Department, Hospital Universitario Central de Asturias, Asturias, Spain.
(12) Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.
(13) Medical Oncology Department, Clínica Universitaria de Navarra, Navarra, Spain.
(14) Medical Oncology Department, Complejo Hospitalario de Navarra, Navarra, Spain.
(15) Oncology, Medical Unit, Merck S.L, an affiliate of Merck KGaA, Darmstadt, Germany.
(16) Anatomopathology Department, Hospital Universitario "Fundación Jimenez Diaz", Madrid, Spain.
(17) Translational Oncology Division, Oncohealth Institute, Hospital Universitario "Fundación Jimenez Diaz", Madrid, Spain.
RESUMEN
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.
CITA DEL ARTÍCULO Sci Rep. 2019 Feb 22;9(1):2589. doi: 10.1038/s41598-019-39291-2
Nuestros autores
