Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients
Por:
Alonso, V, Escudero, P, Fernandez-Martos, C, Salud, A, Mendez, M, Gallego, J, Rodriguez, JR, Martin-Richard, M, Fernandez-Plana, J, Manzano, H, Mendez, JC, Zanui, M, Falco, E, Gil-Raga, M, Rojo, F, Cuatrecasas, M, Feliu, J, Garcia-Albeniz, X, Maurel, J
Publicada:
1 jul 2018
Resumen:
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 N70% 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.
Filiaciones:
Martin-Richard, M:
Hosp Santa Creu & Sant Pau, Med Oncol Serv, Barcelona, Spain.
Garcia-Albeniz, X:
Harvard Sch Publ Hlth, Dept Oncol, Boston, MA USA.
Hosp Univ Miguel Servet, Med Oncol Serv, Zaragoza, Spain.
Hosp Univ Lozano Blesa, Med Oncol Serv, Zaragoza, Spain.
Fdn Inst Valenciano Oncologia, Med Oncol Dept, Valencia, Spain.
Hosp Arnau Vilanova, Med Oncol Serv, Lleida, Spain.
Hosp Mostoles, Med Oncol Serv, Mostoles, Spain.
Univ Elche, Hosp Gen, Med Oncol Serv, Elche, Spain.
Hosp Infanta Cristina, Med Oncol Serv, Badajoz, Spain.
Hosp Mutua Terrasa, Med Oncol Serv, Terrassa, Spain.
Hosp Son Espases, Med Oncol Serv, Palma De Mallorca, Spain.
Ctr Oncol Galicia, Med Oncol Serv, La Coruna, Spain.
Hosp Mataro, Med Oncol Serv, Mataro, Spain.
Hosp Son Llatzer, Med Oncol Serv, Palma De Mallorca, Spain.
Hosp Sagunto, Med Oncol Serv, Sagunto, Spain.
Hosp Fdn Jimenez Diaz, Pathol Serv, Madrid, Spain.
Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain.
Hosp Univ La Paz, Med Oncol Dept, Madrid, Spain.
Univ Barcelona, Translat Genom & Targeted Therapeut Solid Tumors, IDIBAPS, Med Oncol Dept,Hosp Clin Barcelona, Barcelona, Spain.
Gold, Green Published
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