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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
Alonso, V., Escudero, P., Fernández-martos, C., Salud, A., Méndez, M., Gallego, J., Rodriguez, J., Martín-richard, M., Fernández-plana, J., Manzano, H., Méndez, J., Zanui, M., Falcó, E., Gil-raga, M., Rojo, F., Cuatrecasas, M., Feliu, J., García-albéniz, X., & Maurel, J. (2018). 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. https://doi.org/10.1016/j.neo.2018.05.004
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.