Prognostic and predictive impact of consensus molecular subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study.
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Authors
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
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
Document Type
Journal Article
Date
2021-03-03
Date Accepted
2021-02-03
Abstract
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.
Citation
ESMO open, 2021, 6 (2), pp. 100073 - ?
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ELSEVIER
ISSN
2059-7029
eISSN
2059-7029
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Research Team
Systems and Precision Cancer Medicine
Systems and Precision Cancer Medicine
Systems and Precision Cancer Medicine