Thesis etd-10212020-145751 |
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Thesis type
Tesi di specializzazione (5 anni)
Author
BORELLI, BEATRICE
URN
etd-10212020-145751
Thesis title
Prognostic and predictive impacts of Consensus Molecular Subtypes and CRCAssigner classifications in metastatic colorectal cancer: a translational analysis of the TRIBE2 study.
Department
RICERCA TRASLAZIONALE E DELLE NUOVE TECNOLOGIE IN MEDICINA E CHIRURGIA
Course of study
ONCOLOGIA MEDICA
Supervisors
relatore Dott.ssa Cremolini, Chiara
Keywords
- consensus molecular subtypes
- CRCAssigner
- FOLFOXIRI/bevacizumab
- metastatic colorectal cancer
Graduation session start date
10/11/2020
Availability
Withheld
Release date
10/11/2090
Summary
Background:
The Consensus Molecular Subtypes (CMS) demonstrated prognostic value in multiple post-hoc analyses of clinical trials 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 within the context of targeted agents and intensified chemotherapy regimens has not been fully established so far. We investigate the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study.
Patients and Methods:
Among 679 patients randomized in the TRIBE2, 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), progression free survival 2 (PFS2, defined as from time of randomization to second evidence of disease progression) and overall survival (OS).
Results:
Patients with gene expression data available were similar to the overall TRIBE2 population. 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).
Significant interaction effect between CRCA subtypes and treatment arm was demonstrated in terms of PFS (P=0.02), PFS2 (P=0.01) and OS (P=0.008). The benefit of upfront intensified chemotherapy seemed more relevant in the stem-like (PFS, HR=0.60; P=0.03) and mixed subtypes (HR=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 greater benefit from FOLFOXIRI/bevacizumab.
The Consensus Molecular Subtypes (CMS) demonstrated prognostic value in multiple post-hoc analyses of clinical trials 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 within the context of targeted agents and intensified chemotherapy regimens has not been fully established so far. We investigate the prognostic and predictive impact of CMS and CRCA subtypes among mCRC patients treated in the TRIBE2 study.
Patients and Methods:
Among 679 patients randomized in the TRIBE2, 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), progression free survival 2 (PFS2, defined as from time of randomization to second evidence of disease progression) and overall survival (OS).
Results:
Patients with gene expression data available were similar to the overall TRIBE2 population. 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).
Significant interaction effect between CRCA subtypes and treatment arm was demonstrated in terms of PFS (P=0.02), PFS2 (P=0.01) and OS (P=0.008). The benefit of upfront intensified chemotherapy seemed more relevant in the stem-like (PFS, HR=0.60; P=0.03) and mixed subtypes (HR=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 greater benefit from FOLFOXIRI/bevacizumab.
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