# Impact of consensus molecular subtype on survival in patients with metastatic colorectal cancer: results from CALGB/SWOG 80405

Source: https://onco.cc/key-papers/paper-lenz-cms-calgb-swog-80405-jco-2019/  
OnCo record `paper-lenz-cms-calgb-swog-80405-jco-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In the one randomised trial where the four gene-activity subtypes were measured, they predicted not only how long people lived but which biological drug worked better: the immune subtype did better with bevacizumab and the canonical subtype with cetuximab.

## Summary

The consensus molecular subtypes were characterised with a NanoString gene expression panel on primary tumours from 581 patients enrolled in CALGB/SWOG 80405, a phase 3 trial comparing the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin and oxaliplatin or irinotecan as first-line treatment of advanced colorectal cancer. The subtypes were highly prognostic for overall survival (p less than 0.001) and progression-free survival (p less than 0.001), and predictive for both (interaction p less than 0.001 for overall survival and 0.0032 for progression-free survival). In the CMS1 cohort, patients treated with bevacizumab lived significantly longer than those treated with cetuximab (p less than 0.001); in the CMS2 cohort, patients treated with cetuximab lived significantly longer than those treated with bevacizumab (p = 0.0046).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Journal of Clinical Oncology
- Year: 2019
- DOI: 10.1200/JCO.18.02258
- Authors: Lenz HJ, Ou FS, Venook AP, et al.
- Findings: Consensus molecular subtypes prognostic for overall and progression-free survival (p less than 0.001).; CMS1: longer overall survival with bevacizumab than cetuximab (p less than 0.001).; CMS2: longer overall survival with cetuximab than bevacizumab (p = 0.0046).
- What it means: It is the strongest evidence that the consensus subtypes could choose between the two first-line biologicals, and the clearest statement of why they have not: it is a retrospective analysis of a subset of one trial, on an assay nobody has validated for clinical use.
- Caveats: Retrospective on 581 of the trial's patients, so subgroup effects may be chance.; Primary tumour tissue and bulk RNA, with the stromal confound described by Isella and Calon.; No prospective subtype-directed trial has been run.

## Sources

- Lenz et al., J Clin Oncol 2019: consensus molecular subtype and survival in 581 CALGB/SWOG 80405 patients: https://doi.org/10.1200/JCO.18.02258
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31042420/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [Cetuximab](https://onco.cc/drugs/cetuximab/)
- terms: [Consensus molecular subtypes (CMS1-4)](https://onco.cc/terms/cms-subtypes/)
- people: [Alan P. Venook](https://onco.cc/people/alan-venook/), [Heinz-Josef Lenz](https://onco.cc/people/heinz-josef-lenz/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)

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