Advertisement

ESMO 2019: ctDNA as a Marker for Disease-Free Survival With Oxaliplatin Treatment in Stage III Colon Cancer


Advertisement
Get Permission

Patients with advanced colon cancer and plasma samples containing circulating tumor DNA (ctDNA) were less likely to achieve 2-year disease-free survival with oxaliplatin-based adjuvant treatment than patients with ctDNA-negative samples, according to findings presented at the European Society for Medical Oncology (ESMO) 2019 Congress (Abstract LBA30). Both patient cohorts responded more favorably to 6 months of adjuvant treatment.

Presenting author Julien Taieb, MD, PhD, of Hopital European George Pompidou, remarked in a statement that the predictive value of ctDNA was unknown for adjuvant treatment, which prompted this analysis of ctDNA from patients participating in the IDEA-FRANCE trial, which investigated 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer. The aim of this analysis was to determine the prognostic and predictive value of ctDNA for adjuvant treatment duration lasting 3 vs 6 months.

Methods

The investigators tested ctDNA using 2 methylated markers—WIF1 and NPY—by digital droplet polymerase chain reaction accordingly to a method developed and validated for colorectal cancer. Comparisons regarding tumor characteristics and disease-free survival were done between patients with ctDNA-positive and -negative samples in the 6- and 3-month treatment arms and reported at ESMO 2019 Congress. Comparison between the ctDNA-tested patients and the full study population and disease-free survival are ongoing, as are preplanned subgroup analyses for high- and low-risk patients.

A total of 1,345 of 2,010 patients consenting to the IDEA translational research program had available blood sample for ctDNA testing. Of these, 805 patients were sampled prior to initiation of chemotherapy and fully analyzed. This patient population had more performance status 0 (77% vs 71%) and more stage T4 tumors and/or N2 status (28% vs 23%) than the remaining 1,205 consenting patients.

Results of ctDNA Analysis

From the 805 samples, 696 were ctDNA-negative and 109 were ctDNA-positive. Analysis of these samples and a comparison of patients with ctDNA-positive and ctDNA-negative samples indicated that patients with ctDNA-positive samples had more advanced tumors that included characteristics such as stage T4, poor differentiation, and tumor perforation.

KEY POINTS

  • The 2-year disease-free survival rates in patients with ctDNA-positive samples was 64% vs 82% in patients with ctDNA-negative samples.
  • In both cohorts of patients, adjuvant oxaliplatin treatment carried out for 6 months produced better outcomes than treatment for 3 months.

The 2-year disease-free survival rates in patients with ctDNA-positive samples was 64% vs 82% in patients with ctDNA-negative samples (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 1.25–2.45; P = .001).

Multivariate analysis including variables of age, sex, microsatellite instability (MSI) status, tumor perforation, T stage, N stage, and treatment arm confirmed the presence of ctDNA as an independent prognostic marker (adjusted HR = 1.85, 95% CI = 1.31–2.61; P < .001).

Adjuvant oxaliplatin treatment carried out for 6 months produced better outcomes than treatment for 3 months in both patients with ctDNA-negative samples (HR = 0.69, 95% CI = 0.52–0.93; P = .015) as well as patients with ctDNA-positive samples (HR = 0.50, 95% CI = 0.27–0.95; P = .033).

The authors concluded, “In this first ctDNA assessment on a large series coming from a phase III clinical trial, we found 13.5% of patients with ctDNA postsurgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of [oxaplatin] treatment seems better in both ctDNA-positive and -negative patients. ctDNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.”

Disclosure: Funding for the trial was provided by INCa, GERCOR and funding for the translational project was provided by ARC (Association de Recherche contre le Cancer). For full disclosures of the study authors, visit esmo.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®.
Advertisement

Advertisement



Advertisement