Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients
Alonso, Vicente (Hospital Universitario Miguel Servet (Saragossa))
Escudero, Pilar (Hospital Clínico Universitario Lozano Blesa)
Fernández-Martos, Carlos (Fundación Instituto Valenciano de Oncologia)
Salud, Antonia (Hospital Universitari Arnau de Vilanova)
Méndez, Miguel (Hospital Universitario de Móstoles (Madrid))
Gallego, Javier (Hospital General Universitario de Elche)
Rodriguez, Jose Ramon (Hospital Infanta Cristina)
Martín-Richard, Marta (Institut d'Investigació Biomèdica Sant Pau)
Fernández Plana, Julen (Hospital Mutua de Terrasa)
Manzano, Hermini (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Méndez Méndez, José Carlos (Centro Oncologico de Galicia)
Zanui, Montserrat (Hospital de Mataró. Consorci Sanitari del Maresme)
Falcó, Esther (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears))
Gil-Raga, Mireia (Hospital de Sagunto)
Rojo, Federico (Hospital Fundación Jiménez Díaz)
Cuatrecasas, Miriam (Hospital Clínic i Provincial de Barcelona)
Feliu, Jaime (Hospital Universitario La Paz (Madrid))
Garcia-Albeniz, Xabier (Harvard School of Public Health)
Maurel, Joan (Hospital Clínic i Provincial de Barcelona)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	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. 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. 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). 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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Neoplasia (New York, N.Y.), Vol. 20 Núm. 7 (july 2018) , p. 678-686, ISSN 1476-5586

DOI: 10.1016/j.neo.2018.05.004
PMID: 29842993

9 p, 418.0 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles