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October 04, 2019
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Circulating tumor DNA ‘a major prognostic factor’ in colorectal cancer

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BARCELONA, Spain — Circulating tumor DNA detected through liquid biopsy appeared to be an independent prognostic marker for identifying patients with colorectal cancer who are likely to relapse after surgery, according to results of a phase 3 trial presented at European Society for Medical Oncology Congress.

The results also showed that 6 months of adjuvant treatment may be superior to 3 months for this patient population, regardless of circulating tumor DNA (ctDNA) status.

“In this large prospective trial, we confirmed that ctDNA is an independent prognostic factor in colorectal cancer and that approximately six out of 10 patients who are ctDNA-positive will remain disease-free 2 years after standard adjuvant chemotherapy, compared with 8 out of 10 of those who are ctDNA-negative,” Julien Taieb, MD, professor of medicine at Paris Desartes University in France, said in a press release. “ctDNA testing did not predict which patients should have 3 or 6 months of adjuvant chemotherapy, and there is continuing debate over the optimal type and duration of treatment for patients who are ctDNA-positive, but we now know that ctDNA is a major prognostic factor that will be very useful in stratifying patients and driving future trials of colorectal cancer.”

Taieb and colleagues analyzed plasma samples of 805 patients from the IDEA-FRANCE trial who underwent liquid biopsy before adjuvant chemotherapy for stage III colorectal cancer.

Of the patients sampled, 109 (13.5%) had ctDNA in their blood.

Patients with ctDNA appeared more likely to have T4 disease, poor differentiation and tumor perforation.

Researchers sought to determine the prognostic value of ctDNA as well as its predictive value for adjuvant treatment duration.

Results showed 2-year DFS of 64% for ctDNA-positive patients compared with 82% for ctDNA-negative patients (HR = 1.75; 95% CI, 1.25-2.45).

A multivariate analysis that accounted for age, gender, microsatellite instability, perforation, T-stage, N-stage and treatment group confirmed ctDNA as an independent prognostic marker (HR = 1.85; 95% CI, 1,31-2.61).

Researchers also analyzed DFS according to ctDNA results among patients who received adjuvant chemotherapy (90% FOLFOX) for 6 months vs. 3 months.

Results showed 6 months of adjuvant chemotherapy was superior to 3 months for both patients who were ctDNA-negative (HR = 0.69; 95% CI, 0.52-0.93) and ctDNA-positive (HR = 0.5; 95% CI, 0.27-0.95). Researchers noted that ctDNA-positive patients treated for 6 months had a prognosis similar to that of ctDNA-negative patients treated for 3 months.

"When patients have surgery for early stage colorectal cancer, doubts remain as to whether the disease has been completely eradicated and, as a result, patients often receive adjuvant chemotherapy,” Alberto Bardelli, PhD, director of laboratory molecular oncology at Candiolo Cancer Institute and professor of oncology at University of Turin in Italy, said in a press release. “However, the IDEA-FRANCE results have shown we can now use a blood test to say whether the patient is clear or not." – by John DeRosier

Reference:

Taieb J, et al. Abstract LBA30_PR. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.

Disclosures: Taieb reports honoraria from and consultant and speakers’ bureau roles with Amgen, Eli Lilly, Merck, Pierre Fabre, Sanofi and Servier. Please see the abstract for all other authors’ relevant financial disclosures.