Author: admin

In a study reported in the Journal of Clinical Oncology, Sinicrope et al found that a tissue-free circulating tumor DNA (ctDNA) assay had strong prognostic value in patients receiving FOLFOX (fluorouracil, leucovorin, and oxaliplatin)-based adjuvant therapy for stage III colorectal cancer.

Study Details

The study used data from 2,260 evaluable patients with stage III disease receiving FOLFOX-based adjuvant therapy in the phase III Alliance N0147 trial. Plasma samples collected after surgery and before adjuvant FOLFOX alone or with cetuximab were assessed by tissue-free ctDNA assay. In ctDNA-positive patients, tumor fraction (TF) was quantified and genotyping was performed with a 739-gene panel.

Key Findings

Among the 2,260 patients, 461 (20.4%) were ctDNA-positive; significantly higher positivity rates were found among advanced T-/N-stage, high-grade, obstruction/perforation, and BRAF V600E–mutant tumors.

At a median follow-up of 6.1 years, ctDNA positivity was independently associated (all P < .0001) with poorer time to recurrence (hazard ratio [HR] = 5.96, 95% confidence interval [CI] = 5.11–6.96), disease-free survival (HR = 5.03, 95% CI = 4.36–5.81), and overall survival (HR = 4.45, 95% CI = 3.76–5.27). For the ctDNA-positive group vs the ctDNA-negative group, 5-year disease-free survival was 27.7% vs 77.1 and 5-year overall survival was 50.4% vs 86.8%. The adverse prognostic impact of ctDNA positivity was greater in lower T/N stage, low-risk, and deficient mismatch repair subgroups (interaction P = .0012–.041).

Among ctDNA-positive patients, TF was approximately twice that in those with recurrence or death (P = .0002), and TN-stratified patients for time to recurrence, disease-free survival, and overall survival (all adjusted P < .002). On genotyping, mutations in FLT1 (odds ratio [OR] = 8.99) and PREX2 (OR = 7.73) were the most strongly associated with recurrence (P < .03).

The investigators concluded: “Evaluation of ctDNA in resected stage III [colorectal cancer] using a tissue-free assay provided robust and independent prognostic value. Higher ctDNA burden, [deficient mismatch repair], and specific mutations defined poor prognostic groups among ctDNA-positive patients.”

Frank A. Sinicrope, MD, of the Department of Oncology, Mayo Clinic, Rochester, Minnesota, is the corresponding author for the Journal of Clinical Oncology article.

DISCLOSURE: The study was supported by the Mayo Foundation for Research and Education and Guardant Health, Inc. For full disclosures of the study authors, visit ascopubs.org.