Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance).

Journal Article (Clinical Trial, Phase III;Journal Article)

PURPOSE: To determine the predictive and prognostic value of the consensus molecular subtypes (CMSs) of colorectal cancer (CRC) that represent a merging of gene expression-based features largely in primary tumors from six independent classification systems and provide a framework for capturing the intrinsic heterogeneity of CRC in patients enrolled in CALGB/SWOG 80405. PATIENTS AND METHODS: CALGB/SWOG 80405 is a phase III trial that compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced CRC. We characterized the CMS classification using a novel NanoString gene expression panel on primary CRCs from 581 patients enrolled in this study to assess the prognostic and predictive value of CMSs in these patients. RESULTS: The CMSs are highly prognostic for overall survival (OS; P < .001) and progression-free survival (PFS; P < .001). Furthermore, CMSs were predictive for both OS (P for interaction < .001) and PFS (P for interaction = .0032). In the CMS1 cohort, patients treated with bevacizumab had a significantly longer OS than those treated with cetuximab (P < .001). In the CMS2 cohort, patients treated with cetuximab had a significantly longer OS than patients treated with bevacizumab (P = .0046). CONCLUSION: These findings highlight the possible clinical utility of CMSs and suggests that refinement of the CMS classification may provide a path toward identifying patients with metastatic CRC who are most likely to benefit from specific targeted therapy as part of the initial treatment.

Full Text

Duke Authors

Cited Authors

  • Lenz, H-J; Ou, F-S; Venook, AP; Hochster, HS; Niedzwiecki, D; Goldberg, RM; Mayer, RJ; Bertagnolli, MM; Blanke, CD; Zemla, T; Qu, X; Wirapati, P; Tejpar, S; Innocenti, F; Kabbarah, O

Published Date

  • August 1, 2019

Published In

Volume / Issue

  • 37 / 22

Start / End Page

  • 1876 - 1885

PubMed ID

  • 31042420

Pubmed Central ID

  • PMC6675593

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.18.02258


  • eng

Conference Location

  • United States