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Title: The prognostic impact of Consensus Molecular Subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial.
Austin Authors: Mooi, Jennifer K ;Wirapati, P;Asher, R;Lee, C K;Savas, P S;Price, T J;Townsend, A;Hardingham, J;Buchanan, D;Williams, D ;Tejpar, S;Mariadason, John M ;Tebbutt, Niall C 
Affiliation: Oncology, University Hospital Leuven, Leuven, BELGIUM
Oncology, The Queen Elizabeth Hospital, Basil Hetzel Institute, University of Adelaide, Woodville, SA, AUSTRALIA
Colorectal Oncogenomics Group, The University of Melbourne, Genetic Epidemiology Laboratory, Department of Pathology, Royal Melbourne Hospital, Parkville, VIC, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Bioinformatics Core Facility, Swiss Institute of Bioinformatics, LaUSAnne, SWITZERLAND
NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, AUSTRALIA
Peter MacCallum Cancer Center, Melbourne, VIC, AUSTRALIA
Medical Oncology, The Queen Elizabeth Hospital and University of Adelaide, Woodville, SA, AUSTRALIA
Issue Date: 1-Nov-2018
Date: 2018-09-21
Publication information: Annals of oncology : official journal of the European Society for Medical Oncology 2018; 29(11): 2240-2246
Abstract: The Consensus Molecular Subtypes (CMS) is a transcriptome-based classification of colorectal cancer (CRC) initially described in early-stage cohorts, but the associations of CMS with treatment outcomes in the metastatic setting are yet to be established. This study aimed to evaluate the prognostic impact of CMS classification and its predictive effects for bevacizumab benefit in metastatic CRC by correlative analysis of the AGITG MAX trial. The MAX trial previously reported improved progression-free survival (PFS) for the addition of bevacizumab (B) to chemotherapy (capecitabine (C) +/- mitomycin (M)). Archival primary tumours from 237 patients (50% of trial population) underwent gene expression profiling and classification into CMS groups. CMS groups were correlated to PFS and overall survival (OS). The interaction of CMS with treatment was assessed by proportional hazards model. The distribution of CMS in MAX were: CMS1 18%, CMS2 47%, CMS3 12%, CMS4 23%. CMS1 was the predominant subtype in right-sided primary tumours, while CMS2 was the predominant subtype in left-sided. CMS was prognostic of overall survival (OS) (P=0.008), with CMS2 associated with the best outcome and CMS1 the worst. CMS remained an independent prognostic factor in a multivariate analysis. There was a significant interaction between CMS and treatment (P-interaction=0.03), for PFS, with hazard ratios (95% CI) for CB+CBM versus C arms in CMS 1,2,3 and 4: 0.83 (0.43-1.62), 0.50 (0.33-0.76), 0.31 (0.13-0.75) and 1.24 (0.68-2.25) respectively. This exploratory study found that CMS stratified OS outcomes in metastatic CRC regardless of first-line treatment, with prognostic effects of CMS groups distinct from those previously reported in early-stage cohorts. In CMS associations with treatment, CMS2 and possibly CMS3 tumours may preferentially benefit from the addition of bevacizumab to first-line capecitabine-based chemotherapy, compared to other CMS groups. Validation of these findings in additional cohorts is warranted. This is a molecular sub-study of MAX clinical trial (NCT00294359).
DOI: 10.1093/annonc/mdy410
Journal: Annals of oncology : official journal of the European Society for Medical Oncology
PubMed URL: 30247524
Type: Journal Article
Appears in Collections:Journal articles

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