Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper 1 – Gastrointestinal tumours, colorectal

5478 - Analysis of circulating tumor DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: prognostic and predictive value for adjuvant treatment duration

Date

28 Sep 2019

Session

Proffered Paper 1 – Gastrointestinal tumours, colorectal

Topics

Cancer Biology

Tumour Site

Colon and Rectal Cancer

Presenters

Julien Taieb

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

J. Taieb1, V. Taly2, D. Vernerey3, C. bourreau2, J. Bennouna4, R. Faroux5, J. Desrame6, O. Bouche7, C. Borg8, J. Egreteau9, L. Mineur10, C. LEPERE11, G. Deplanque12, C. mulot2, C. Louvet13, M. Mabro14, M. Ychou15, A. de Gramont16, T. Andre17, P. Laurent-Puig2

Author affiliations

  • 1 Department Of Gastroenterology And Digestive Oncology, European Georges Pompidou Hospital, 75015 - Paris/FR
  • 2 Sorbonne Université, Uspc, Université Paris Descartes, Université Paris Diderot, Centre de Recherche des Cordeliers, INSERM, CNRS, 75006 - Paris/FR
  • 3 Methodology And Quality Of Life Unit In Oncology (umqvc), University Hospital of Besançon, 25000 - Besançon/FR
  • 4 Digestive And Lung Oncology Department, Nantes University Hospital, 44093 - Nantes/FR
  • 5 Gastroenterology And Hepatology, CHD Vendee - Hopital Les Oudairies, 85925 - La Roche sur Yon/FR
  • 6 Medical Oncology, Hôpital privé Jean Mermoz, 69373 - Lyon/FR
  • 7 Gastroenterology, CHU de Reims - Hôpital Robert Debré, 51092 - Reims/FR
  • 8 Department Of Medical Oncology, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 9 Oncology, CH Sud Bretagne, 56322 - Lorient/FR
  • 10 Radiotherapy And Oncology Gi And Liver, Institut Ste Catherine, Avignon/FR
  • 11 Gi Oncology, European George Pompidou Hospital, 75015 - Paris/FR
  • 12 Oncologie Médicale, Hôpital Riviera-Chablais, 1800 - Vevey/CH
  • 13 Oncologie Médicale, Institut Mutualiste Montsouris, 75014 - Paris/FR
  • 14 Oncology, Hopital Foch, 92151 - Suresnes/FR
  • 15 Ircm (institute Of Cancer Research Of Montpellier), ICM Regional Cancer Institute of Montpellier, 34090 - Montpellier/FR
  • 16 Oncology, Institut hospitalier Franco-Britannique, 92300 - Levallois-Perret/FR
  • 17 Medical Oncology, Hopital Saint-Antoine, 75571 - Paris/FR

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

LBA30_PR: Analysis of circulating tumor DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: prognostic and predictive value for adjuvant treatment duration, by Julien Taieb

Abstract 5478

Background

ctDNA has been recently suggested as a major prognostic factor in resected stage II and III colon cancer patients (pts)1,2. Its predictive value for adjuvant treatment intensity or duration is currently unknown. We have analyzed here ctDNA from pts enrolled in the IDEA-FRANCE trial3, its prognostic value and its predictive value for treatment duration (3 or 6 months).

Methods

ctDNA was tested by using the detection of 2 methylated markers (WIF1 and NPY) by digital droplet PCR accordingly to a method developed and validated for colorectal cancer 4-6. Comparisons for pts and tumour characteristics and DFS will be done between the ctDNA tested pts and the full study population and between ctDNA positive and negative pts. DFS has been analyzed in the 6 and 3M treatment arms according to ctDNA results. Subgroup analyses for high- and low-risk pts were pre-planned.

Results

Of the 1345/2010 pts that consented to the IDEA translational research program, with available blood sample for ctDNA testing, 805 have been sampled before chemotherapy start and fully analyzed. More PS 0 (77% vs 71%) and more T4 and/or N2 (28% vs 23%) were observed in the 805 pts studied here than in the 1205 pts left. 696 pts were found ctDNA- and 109 ctDNA + (13.5%). ctDNA+ pts were more often T4, poorly differentiated and with tumour perforation. 2-year DFS was 64% vs 82% in ctDNA+ and – pts, respectively (HR :1.75 (95%CI 1.25-2.45) p = 0.001). In multivariate analysis including Age, Gender, MSI, perforation, T stage, N stage and treatment arm, ctDNA was confirmed as an independent prognostic marker (adj.HR: 1.85 (95%CI 1.31 to 2.61) p < 0.001). Adjuvant treatment for 6 months was superior to 3 months in both ctDNA– (HR :0.69 (95%CI 0.52 to 0.93) p = 0.015) and ctDNA+ pts (HR: 0.50 (95%CI 0.27 to 0.95) p = 0.033). Interestingly ctDNA+ pts treated 6 months had a similar prognosis to ctDNA- pts treated 3 months.

Conclusions

In this first ctDNA assessment on a large series coming from a phase III clinical trial we found 13.5% of pts with ctDNA post-surgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of treatment seems better in both ctDNA+ and- pts. [1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92. [2]Schøler LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. [3] André T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477. [4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139. [5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425. [6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219.

Clinical trial identification

NCT00958737.

Editorial acknowledgement

[1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92.

[2]Schøler LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445.

[3] André T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477.

[4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139.

[5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425.

[6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219.

Legal entity responsible for the study

Gercor-Prodige.

Funding

Clinical trial: INCa, GERCOR; Translational project: ARC (Association de Recherche contre le Cancer, Paris, France).

Disclosure

J. Taieb: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: pierre fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi. D. Vernerey: Honoraria (self), Advisory / Consultancy: HalioDX; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Janssen. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.