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Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study
INTRODUCTION: The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103536/ https://www.ncbi.nlm.nih.gov/pubmed/33676295 http://dx.doi.org/10.1016/j.esmoop.2021.100073 |
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author | Borelli, B. Fontana, E. Giordano, M. Antoniotti, C. Lonardi, S. Bergamo, F. Pietrantonio, F. Morano, F. Tamburini, E. Boccaccino, A. Santini, D. Zucchelli, G. Pella, N. Maiello, E. Passardi, A. Zaniboni, A. Ugolini, C. Fontanini, G. Falcone, A. Nyamundanda, G. Sadanandam, A. Cremolini, C. |
author_facet | Borelli, B. Fontana, E. Giordano, M. Antoniotti, C. Lonardi, S. Bergamo, F. Pietrantonio, F. Morano, F. Tamburini, E. Boccaccino, A. Santini, D. Zucchelli, G. Pella, N. Maiello, E. Passardi, A. Zaniboni, A. Ugolini, C. Fontanini, G. Falcone, A. Nyamundanda, G. Sadanandam, A. Cremolini, C. |
author_sort | Borelli, B. |
collection | PubMed |
description | INTRODUCTION: The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard to the choice of the first-line therapy has not been established. We investigated the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study. METHODS: Among 679 randomized patients, 426 and 428 (63%) samples were profiled according to CMS and CRCA classifications, respectively. The prognostic and predictive impact of both CMS and CRCA subtypes was investigated with univariate and multivariate analyses for progression-free survival (PFS), PFS 2 (PFS2), and overall survival (OS). RESULTS: Significant associations of CMS and CRCA subtypes with PFS, PFS2, and OS were demonstrated; the CMS classifier confirmed its independent prognostic value in the multivariable model (P value for PFS/PFS2/OS = 0.01/0.07/0.08). The effect of treatment intensification was independent of CMS subtypes (P value for interaction for PFS/PFS2/OS = 0.88/0.75/0.55). A significant interaction effect between CRCA subtypes and treatment arm was demonstrated in PFS (P = 0.02), PFS2 (P = 0.01), and OS (P = 0.008). The benefit of FOLFOXIRI seemed more relevant in the stem-like (PFS, hazard ratio = 0.60; P = 0.03) and mixed subtypes (hazard ratio = 0.44; P = 0.002). These findings were confirmed in a subgroup of patients of the previous TRIBE study. CONCLUSIONS: We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/bevacizumab. |
format | Online Article Text |
id | pubmed-8103536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-81035362021-05-14 Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study Borelli, B. Fontana, E. Giordano, M. Antoniotti, C. Lonardi, S. Bergamo, F. Pietrantonio, F. Morano, F. Tamburini, E. Boccaccino, A. Santini, D. Zucchelli, G. Pella, N. Maiello, E. Passardi, A. Zaniboni, A. Ugolini, C. Fontanini, G. Falcone, A. Nyamundanda, G. Sadanandam, A. Cremolini, C. ESMO Open Original Research INTRODUCTION: The consensus molecular subtypes (CMS) demonstrated prognostic value in metastatic colorectal cancer (mCRC). Similarly, a prognostic impact was suggested for the pre-consensus CRCAssigner (CRCA) classifier in early stages. The potential predictive role of these classifiers with regard to the choice of the first-line therapy has not been established. We investigated the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study. METHODS: Among 679 randomized patients, 426 and 428 (63%) samples were profiled according to CMS and CRCA classifications, respectively. The prognostic and predictive impact of both CMS and CRCA subtypes was investigated with univariate and multivariate analyses for progression-free survival (PFS), PFS 2 (PFS2), and overall survival (OS). RESULTS: Significant associations of CMS and CRCA subtypes with PFS, PFS2, and OS were demonstrated; the CMS classifier confirmed its independent prognostic value in the multivariable model (P value for PFS/PFS2/OS = 0.01/0.07/0.08). The effect of treatment intensification was independent of CMS subtypes (P value for interaction for PFS/PFS2/OS = 0.88/0.75/0.55). A significant interaction effect between CRCA subtypes and treatment arm was demonstrated in PFS (P = 0.02), PFS2 (P = 0.01), and OS (P = 0.008). The benefit of FOLFOXIRI seemed more relevant in the stem-like (PFS, hazard ratio = 0.60; P = 0.03) and mixed subtypes (hazard ratio = 0.44; P = 0.002). These findings were confirmed in a subgroup of patients of the previous TRIBE study. CONCLUSIONS: We confirmed the independent prognostic role of CMS classification in mCRC independently of RAS/BRAF status. CRCA classification may help identifying subgroups of patients who may derive more benefit from FOLFOXIRI/bevacizumab. Elsevier 2021-03-03 /pmc/articles/PMC8103536/ /pubmed/33676295 http://dx.doi.org/10.1016/j.esmoop.2021.100073 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Borelli, B. Fontana, E. Giordano, M. Antoniotti, C. Lonardi, S. Bergamo, F. Pietrantonio, F. Morano, F. Tamburini, E. Boccaccino, A. Santini, D. Zucchelli, G. Pella, N. Maiello, E. Passardi, A. Zaniboni, A. Ugolini, C. Fontanini, G. Falcone, A. Nyamundanda, G. Sadanandam, A. Cremolini, C. Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study |
title | Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study |
title_full | Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study |
title_fullStr | Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study |
title_full_unstemmed | Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study |
title_short | Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study |
title_sort | prognostic and predictive impact of consensus molecular subtypes and crcassigner classifications in metastatic colorectal cancer: a translational analysis of the tribe2 study |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103536/ https://www.ncbi.nlm.nih.gov/pubmed/33676295 http://dx.doi.org/10.1016/j.esmoop.2021.100073 |
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