| Title: |
Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer |
| Authors: |
Borrero-Palacios, A.; Cebrián, A.; Gómez del Pulgar, M. T.; García-Carbonero, R.; García, P.; Aranda, E.; Elez, E.; López-López, R.; Cervantes, A.; Valladares, M.; Nadal, C.; Viéitez, J. M.; Guillén-Ponce, C.; Rodríguez, J.; Hernández, I.; García, J. L.; Vega-Bravo, R.; Puime-Otin, A.; Martínez-Useros, J.; Del Puerto-Nevado, L.; Rincón, R.; Rodríguez-Remírez, M.; Rojo, F.; García-Foncillas López, Jesús Miguel |
| Contributors: |
Departamento de Medicina; Facultad de Medicina; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) |
| Publisher Information: |
Nature Research (part of Springer Nature) |
| Publication Year: |
2019 |
| Collection: |
Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| Subject Terms: |
KIR2DS4; Cetuximab; Metastatic colorectal cancer; Polymorphism FcγRIIIa V158F; Combination; Medicina |
| Description: |
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. ; This clinical trial was approved and supported by Merck S.L., an affiliate of Merck KGaA, Darmstadt. Germany [research project number 2010-023580-18, date: 05-06-2014] |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Scientific Reports; https://doi.org/10.1038/s41598-019-39291-2; Scientific Reports 9 (2019): 2589; https://hdl.handle.net/10486/688580 |
| DOI: |
10.1038/s41598-019-39291-2 |
| Availability: |
https://hdl.handle.net/10486/688580; https://doi.org/10.1038/s41598-019-39291-2 |
| Rights: |
© 2019, The Author(s) ; Reconocimiento ; open access |
| Accession Number: |
edsbas.ECF61721 |
| Database: |
BASE |