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Molecular Diagnosis & Therapy
Erschienen in: Molecular Diagnosis & Therapy 6/2015

01.12.2015 | Original Research Article

Prognostic Value of BRAF, PI3K, PTEN, EGFR Copy Number, Amphiregulin and Epiregulin Status in Patients with KRAS Codon 12 Wild-Type Metastatic Colorectal Cancer Receiving First-Line Chemotherapy with Anti-EGFR Therapy

verfasst von: Patricia Llovet, Javier Sastre, Julián Sanz Ortega, Inmaculada Bando, Milagros Ferrer, Pilar García-Alfonso, Olga Donnay, Alfredo Carrato, Ana Jiménez, Enrique Aranda, Ana León, Cristina Grávalos, Juan Carlos Cámara, Jaime Feliú, Bárbara Sanchíz, Trinidad Caldés, Eduardo Díaz-Rubio

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 6/2015

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Abstract

Introduction

Mutational analysis of RAS is required for anti-epidermal growth factor receptor (EGFR) treatment for patients with metastatic colorectal cancer (mCRC). However, most patients with KRAS wild-type tumors still do not respond. Other molecules downstream of the EGFR may also play a role in resistance to EGFR therapies.

Objective

Our objective was to investigate the clinical importance of biomarkers in relation to response, progression-free survival, and overall survival in patients with mCRC receiving first-line treatment with anti-EGFR therapy plus chemotherapy.

Methods

We studied the EGFR pathway [EGFR, NRAS, BRAF, PIK3CA, phosphatase and tensin homolog (PTEN), amphiregulin (AREG), and epiregulin (EREG)] in 105 patients with mCRC KRAS codon 12 wild type. We analysed objective response, progression-free survival, and overall survival in molecularly defined subgroups of the patients receiving anti-EGFR therapy plus chemotherapy as first-line treatment.

Results

We found a significant association between RAS wild-type, BRAF wild-type, EREG, and AREG overexpression and response to anti-EGFR therapy (p = 0.003, p = 0.015, p = 0.05, and p = 0.009, respectively). Progression-free survival and overall survival were lower in patients with RAS (p = 0.36 and p ≤ 0.001, respectively) or BRAF (p = 0.003 and p = 0.002, respectively) mutant tumors. Patients with EREG and AREG messenger RNA (mRNA) expression had longer survival than those with low-expression tumors; progression-free survival and overall survival were significant for AREG (p = 0.001 and p = 0.05, respectively). Patients with EGFR amplification tumors responded better to treatment and had better survival rates, although this was not significant. PIK3CA and PTEN were not associated with either response or survival. The multivariate logistic regression model for response showed only BRAF as a significant predictor after adjustment for the other covariates (p = 0.04, odds ratio 8.3, 95 % confidence interval 0.81–86.0).

Conclusions

RAS, BRAF, AREG, and EREG predict for efficacy of first-line anti-EGFR therapy in patients with mCRC.
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Metadaten
Titel
Prognostic Value of BRAF, PI3K, PTEN, EGFR Copy Number, Amphiregulin and Epiregulin Status in Patients with KRAS Codon 12 Wild-Type Metastatic Colorectal Cancer Receiving First-Line Chemotherapy with Anti-EGFR Therapy
verfasst von
Patricia Llovet
Javier Sastre
Julián Sanz Ortega
Inmaculada Bando
Milagros Ferrer
Pilar García-Alfonso
Olga Donnay
Alfredo Carrato
Ana Jiménez
Enrique Aranda
Ana León
Cristina Grávalos
Juan Carlos Cámara
Jaime Feliú
Bárbara Sanchíz
Trinidad Caldés
Eduardo Díaz-Rubio
Publikationsdatum
01.12.2015
Verlag
Springer International Publishing
Erschienen in
Molecular Diagnosis & Therapy / Ausgabe 6/2015
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI
https://doi.org/10.1007/s40291-015-0165-0

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