Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May;132(9):814-821.
doi: 10.1038/s41416-025-02971-0. Epub 2025 Mar 15.

ctDNA variations according to treatment intensity in first-line metastatic colorectal cancer

Adrien Grancher #  1 , Ludivine Beaussire-Trouvay #  2 , Virginie Vernon  1 , Marie Dutherage  1 , Valérie Blondin  3 , Caroline Elie  3 , Karine Bouhier-Leporrier  4 , Marie-Pierre Galais  5 , Tifenn Clabaut  6 , Anne-Laure Bignon  4 , Aurélie Parzy  5 , Alice Gangloff  7 , Lilian Schwarz  8 , Emilie Lévêque  9 , Jean-Christophe Sabourin  10 , Pierre Michel  1 , Nasrin Vasseur  2 , David Sefrioui  1 , André Gilibert  6 , Frédéric Di Fiore  11
Affiliations

ctDNA variations according to treatment intensity in first-line metastatic colorectal cancer

Adrien Grancher et al. Br J Cancer. 2025 May.

Abstract

Background: Circulating tumor DNA variations (∆ctDNA) were reported to be associated with treatment efficacy in metastatic colorectal cancer (mCRC). The present study evaluated ∆ctDNA according to first-line treatment intensity.

Methods: Patients from two prospective ctDNA collections were divided into Group ≤ 2 drugs and Group ≥ 3 drugs. ∆ctDNA were analysed from baseline to cycle 3 or 4 (C3-4) according to three predefined subgroups: ∆ctDNA ≥ 80%_ undetectable, ∆ctDNA ≥ 80%_ detectable, and ∆ctDNA < 80%. Impact of ∆ctDNA on progression-free survival (PFS) and overall survival (OS) were analysed.

Results: Pretreatment ctDNA was detected in 129/152 (84.9%) of patients. A ∆ctDNA ≥ 80%_undetectable was more frequent in Group ≥ 3 than ≤ 2 drugs (respectively 51.5% vs. 32.7%, p = 0.015). Patients with ∆ctDNA ≥ 80%_undetectable had longer survival than other ∆ctDNA subgroups, in Group ≥ 3 drugs (mPFS 11.5 vs 7.8 vs 6.3 months, p = 0.02: mOS 30.2 vs 18.1 vs 16.4 month, p = 0.04) and in Group ≤ 2 drugs (mPFS 8.4 vs 6.0 vs 5.3 months, p = 0.05; mOS 29.6 vs 14.6 vs 14.6 months, p = 0.007).

Discussion: Early ∆ctDNA are associated to treatment intensity in first line mCRC with a significant impact on prognosis.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: This work combine data from two trials, registered on the clinicaltrials.gov website (No. NCT01212510 and NCT02872779), and approved by an ethic committee (Comité de Protection des Personnes Nord-Ouest 1, Rouen University, 76000 France). Each patient included in these two trials gave written consent. The study was performed in accordance with the Declaration of Helsinki.

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49. - PubMed
    1. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol. 2016;27:1386–422. - PubMed
    1. Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75. - PubMed
    1. Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, 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. JAMA. 2017;317:2392–401. - PMC - PubMed
    1. Cremolini C, Antoniotti C, Rossini D, Lonardi S, Loupakis F, Pietrantonio F, et al. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2020;21:497–507. - PubMed

MeSH terms

LinkOut - more resources