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Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients
INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective bio...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030389/ https://www.ncbi.nlm.nih.gov/pubmed/29842993 http://dx.doi.org/10.1016/j.neo.2018.05.004 |
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author | Alonso, Vicente Escudero, Pilar Fernández-Martos, Carlos Salud, Antonia Méndez, Miguel Gallego, Javier Rodriguez, Jose-R. Martín-Richard, Marta Fernández-Plana, Julen Manzano, Hermini Méndez, José-Carlos Zanui, Monserrat Falcó, Esther Gil-Raga, Mireia Rojo, Federico Cuatrecasas, Miriam Feliu, Jaime García-Albéniz, Xabier Maurel, Joan |
author_facet | Alonso, Vicente Escudero, Pilar Fernández-Martos, Carlos Salud, Antonia Méndez, Miguel Gallego, Javier Rodriguez, Jose-R. Martín-Richard, Marta Fernández-Plana, Julen Manzano, Hermini Méndez, José-Carlos Zanui, Monserrat Falcó, Esther Gil-Raga, Mireia Rojo, Federico Cuatrecasas, Miriam Feliu, Jaime García-Albéniz, Xabier Maurel, Joan |
author_sort | Alonso, Vicente |
collection | PubMed |
description | INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. RESULTS: We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). CONCLUSION: A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP. |
format | Online Article Text |
id | pubmed-6030389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60303892018-07-09 Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients Alonso, Vicente Escudero, Pilar Fernández-Martos, Carlos Salud, Antonia Méndez, Miguel Gallego, Javier Rodriguez, Jose-R. Martín-Richard, Marta Fernández-Plana, Julen Manzano, Hermini Méndez, José-Carlos Zanui, Monserrat Falcó, Esther Gil-Raga, Mireia Rojo, Federico Cuatrecasas, Miriam Feliu, Jaime García-Albéniz, Xabier Maurel, Joan Neoplasia Original article INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. RESULTS: We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). CONCLUSION: A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP. Neoplasia Press 2018-05-26 /pmc/articles/PMC6030389/ /pubmed/29842993 http://dx.doi.org/10.1016/j.neo.2018.05.004 Text en © 2018 . Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Alonso, Vicente Escudero, Pilar Fernández-Martos, Carlos Salud, Antonia Méndez, Miguel Gallego, Javier Rodriguez, Jose-R. Martín-Richard, Marta Fernández-Plana, Julen Manzano, Hermini Méndez, José-Carlos Zanui, Monserrat Falcó, Esther Gil-Raga, Mireia Rojo, Federico Cuatrecasas, Miriam Feliu, Jaime García-Albéniz, Xabier Maurel, Joan Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients |
title | Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients |
title_full | Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients |
title_fullStr | Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients |
title_full_unstemmed | Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients |
title_short | Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients |
title_sort | coexpression of p-igf-1r and mmp-7 modulates panitumumab and cetuximab efficacy in ras wild-type metastatic colorectal cancer patients |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030389/ https://www.ncbi.nlm.nih.gov/pubmed/29842993 http://dx.doi.org/10.1016/j.neo.2018.05.004 |
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