Scientific publications

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.

Magazine: Scientific Reports

Date: Feb 20, 2019

Medical Oncology

ABSTRACT

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.

CITATION  Sci Rep. 2019 Feb 22;9(1):2589. doi: 10.1038/s41598-019-39291-2

you mayBE INTERESTED

WHAT TECHNOLOGY
DO WE USE?

The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra

OUR
PROFESSIONALS

The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.

Imagen profesionales de la Clínica Universidad de Navarra

WHY CHOOSE
THE CLINICA?

Learn why we are different from other healthcare centers. Quality, speed, comfort and results.

Imagen del edificio de la Clínica Universidad de Navarra