Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients.
Neoplasia
; 20(7): 678-686, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29842993
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Expressão Gênica
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Receptor IGF Tipo 1
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Proteínas ras
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Metaloproteinase 7 da Matriz
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Cetuximab
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Anticorpos Monoclonais
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article