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Clinical Trial
. 2019 Aug 1;37(22):1876-1885.
doi: 10.1200/JCO.18.02258. Epub 2019 May 1.

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

Heinz-Josef Lenz  1 , Fang-Shu Ou  2 , Alan P Venook  3 , Howard S Hochster  4 , Donna Niedzwiecki  5 , Richard M Goldberg  6 , Robert J Mayer  7 , Monica M Bertagnolli  8 , Charles D Blanke  9 , Tyler Zemla  2 , Xueping Qu  10 , Pratyaksha Wirapati  11 , Sabine Tejpar  12 , Federico Innocenti  13 , Omar Kabbarah  10
Affiliations
Clinical Trial

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

Heinz-Josef Lenz et al. J Clin Oncol. .

Erratum in

  • ERRATA.
    [No authors listed] [No authors listed] J Clin Oncol. 2020 Feb 20;38(6):656. doi: 10.1200/JCO.20.00020. J Clin Oncol. 2020. PMID: 32065856 Free PMC article. No abstract available.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00265850.

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Figures

FIG 1.
FIG 1.
Study flow diagram.
FIG 2.
FIG 2.
Consensus molecular subtype (CMS) proportion. (A) Overall, (B) Right-sided tumors, and (C) left-sided tumors.
FIG 3.
FIG 3.
Overall survival (OS) among patients included in this analysis. CMS, consensus molecular subtype.
FIG 4.
FIG 4.
Overall survival (OS) among patients who received bevacizumab. CMS, consensus molecular subtype.
FIG 5.
FIG 5.
Overall survival (OS) among patients who received cetuximab. CMS, consensus molecular subtype.
FIG A1.
FIG A1.
Progression-free survival (PFS) among patients included in this analysis. CMS, consensus molecular subtype.
FIG A2.
FIG A2.
Progression-free survival (PFS) among patients who received bevacizumab. CMS, consensus molecular subtype.
FIG A3.
FIG A3.
Progression-free survival (PFS) among patients who received cetuximab. CMS, consensus molecular subtype.
See this image and copyright information in PMC

Comment in

References

    1. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62:220–241. - PubMed
    1. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–271. - PubMed
    1. Siegel RL, Miller KD, Fedewa SA, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67:177–193. - PubMed
    1. Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: A randomized clinical trial. JAMA. 2017;317:2392–2401. - PMC - PubMed
    1. Modest DP, Stintzing S, von Weikersthal LF, et al. Exploring the effect of primary tumor sidedness on therapeutic efficacy across treatment lines in patients with metastatic colorectal cancer: Analysis of FIRE-3 (AIOKRK0306) Oncotarget. 2017;8:105749–105760. - PMC - PubMed

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