Alonso, VicenteEscudero, PilarFernandez-Martos, CarlosSalud, AntoniaMendez, MiguelGallego, JavierRodriguez, Jose-RMartin-Richard, MartaFernandez-Plana, JulenManzano, HerminiMendez, Jose-CarlosZanui, MonserratFalcó, EstherGil-Raga, MireiaRojo, FedericoCuatrecasas, MiriamFeliu, JaimeGarcia-Albeniz, XabierMaurel, Joan2024-09-062024-09-062018-07Alonso V, Escudero P, Fernandez-Martos C, Salud A, Mendez M, Gallego J, et al. Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients. Neoplasia. 2018 Jul;20(7):678-86. Epub 2018 May 26.1476-5586http://hdl.handle.net/20.500.13003/17280https://hdl.handle.net/20.500.12105/22516INTRODUCTION: 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.enghttp://creativecommons.org/licenses/by-nc-nd/4.0/AgedKaplan-Meier EstimateAntibodies, MonoclonalHumansMiddle AgedCetuximabMatrix Metalloproteinase 7PrognosisMaleMutationFemaleColorectal NeoplasmsProportional Hazards ModelsProto-Oncogene Proteins B-rafGene ExpressionReceptor, IGF Type 1ras Proteinsresearch articleAttribution-NonCommercial-NoDerivatives 4.0 International29842993207678-68610.1016/j.neo.2018.05.004Neoplasiaopen accessExpresión GénicaModelos de Riesgos ProporcionalesProteínas rasNeoplasias ColorrectalesReceptor IGF Tipo 1FemeninoMetaloproteinasa 7 de la MatrizMutaciónMasculinoProteínas Proto-Oncogénicas B-rafHumanosPersona de Mediana EdadEstimación de Kaplan-MeierPronósticoAncianoAnticuerpos MonoclonalesCetuximab2-s2.0-85047475405436235300004L2000801160