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Impact of Consensus Molecular Subtype on Outcome in Metastatic Colorectal Cancer

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Key Points

  • Consensus molecular subtype classification was significantly prognostic for overall survival.
  • Consensus molecular subtype classification was also significantly prognostic for progression-free survival. 

In a study reported in the Journal of Clinical Oncology, Lenz et al found that consensus molecular subtype of colorectal cancers was highly prognostic for outcomes in patients receiving first-line treatment for advanced disease in the phase III CALGB/SWOG 80405/Alliance trial.

CALGB/SWOG 80405 compared the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin, and oxaliplatin or fluorouracil, leucovorin, and irinotecan as first-line treatment of advanced colorectal cancer. A novel NanoString gene-expression panel was used to determine consensus molecular subtype classification on primary colorectal cancers from 581 patients in the trial. The classification categorizes colorectal cancer into one of four consensus molecular subtype groups: CMS1 = microsatellite instability (MSI)-immune; CMS2 = canonical; CMS3 = metabolic; and CMS4 = mesenchymal.

Impact of Consensus Molecular Subtype Classification

Consensus molecular subtype classification was a significant prognostic marker for overall survival (overall P < .001), with median survival of 15, 40.3, 24.3, and 31.4 months for CMS1, CMS2, CMS3, and CMS4, respectively. Consensus molecular subtype was a significant marker for overall survival among patients receiving bevacizumab in unadjusted analysis, but not in multivariate analysis (P = .2464). Consensus molecular subtype was a significant marker for overall survival in patients who received cetuximab (overall P < .001), with median overall survival of 11.7, 42, 26.8, and 30.8 months for CMS1, CMS2, CMS3, and CMS4, respectively.

In addition, consensus molecular subtype was a significant prognostic marker for progression-free survival in the entire cohort (overall P < .001), among patients receiving bevacizumab (P = .027), and among those receiving cetuximab (P < .001).

The investigators concluded, “These findings highlight the possible clinical utility of consensus molecular subtypes and suggests that refinement of the consensus molecular subtype classification may provide a path toward identifying patients with metastatic colorectal cancer who are most likely to benefit from specific targeted therapy as part of the initial treatment.”

Heinz-Josef Lenz, MD, of the University of Southern California Norris Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants. The trial was supported in part by Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer, and Sanofi. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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