Coexpression of P-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2018 May 30

PMID 29842993

Citations 4

Authors

Vicente Alonso

Pilar Escudero

Carlos Fernandez-Martos

Antonia Salud

Miguel Mendez

Javier Gallego

Jose-R Rodriguez

Marta Martin-Richard

Julen Fernandez-Plana

Hermini Manzano

Jose-Carlos Mendez

Monserrat Zanui

Esther Falco

Mireia Gil-Raga

Federico Rojo

Miriam Cuatrecasas

Jaime Feliu

Xabier Garcia-Albeniz

Joan Maurel

Affiliations

Soon will be listed here.

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.

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