ctDNA Status Predicts Celecoxib Benefit in Stage III Colon Cancer
核心洞察
A subgroup analysis of the CALGB/SWOG 80702 trial reveals that positive circulating tumor DNA (ctDNA (搜索)) status is associated with poorer disease-free survival (DFS) in stage III colon cancer (搜索).
Celecoxib significantly improved DFS outcomes in ctDNA (搜索)-positive patients compared to placebo, suggesting a potential targeted treatment approach.
Patients with ctDNA (搜索)-negative disease showed similar outcomes with celecoxib or placebo, highlighting ctDNA status as a predictive biomarker.
A subgroup analysis of the phase 3 CALGB (Alliance)/SWOG 80702 trial, presented at the 2025 Gastrointestinal Cancers Symposium, has revealed that circulating tumor DNA (ctDNA (搜索)) status can predict the efficacy of celecoxib in patients with stage III resected colon cancer (搜索). The study, led by Dr. Jonathan Nowak from Dana-Farber Cancer Institute, demonstrated that while positive ctDNA status is associated with worse disease-free survival (DFS) overall, celecoxib significantly improved DFS in ctDNA-positive patients compared to placebo.
The trial enrolled patients with resected stage III colon adenocarcinoma and randomly assigned them to receive either celecoxib or placebo in combination with FOLFOX (搜索) (leucovorin calcium, fluorouracil, and oxaliplatin). ctDNA (搜索) analysis was performed retrospectively using the Signatera minimal residual disease assay on banked plasma specimens collected after surgery and before trial enrollment.
Impact of ctDNA Status on Disease-Free Survival
The analysis showed that patients with ctDNA (搜索)-negative colon cancer (搜索) (n = 767) had an estimated 3-year DFS rate of 86.5%. In contrast, patients with ctDNA-positive disease (n = 173) had a significantly lower 3-year DFS rate of 33.7% (P < .0001). This highlights ctDNA status as a strong prognostic marker for DFS in this patient population.
Celecoxib's Benefit in ctDNA-Positive Patients
When stratified by treatment, patients with ctDNA (搜索)-negative disease had similar outcomes regardless of whether they received celecoxib or placebo (3-year DFS rates of 87.4% and 85.6%, respectively). However, among ctDNA-positive patients, celecoxib demonstrated a significant DFS benefit, with 3-year DFS rates of 41.0% compared to 22.6% in the placebo arm (HR, 0.55; 95% CI, 0.39-0.80; P = .0013).
Clinical Implications and Future Directions
"Approximately one-third of patients diagnosed with colon cancer (搜索) have regional lymph node involvement," Dr. Nowak explained. "Despite optimal surgery and adjuvant chemotherapy, approximately 20% to 70% of patients with stage III disease will have a recurrence. Additional strategies beyond standard chemotherapy are needed to reduce risk of recurrent disease and improve survival. One promising option is to use post-resection ctDNA (搜索) status, which can tell us if any residual micrometastatic disease is present in order to help guide adjuvant treatment decisions."
These findings suggest that ctDNA (搜索) status can be used to identify patients who are more likely to benefit from celecoxib as adjuvant therapy. Ongoing sensitivity and subgroup analyses are further evaluating the predictive value of ctDNA for different durations of adjuvant FOLFOX (搜索) in this patient population.