Impact of CAPOX combined with traditional Chinese medicine (TiaoPi AnChang Decoction) on disease-free survival in patients with stage III or high-risk stage II colorectal cancer: An updated report of a randomized, double-blind, placebo-controlled tri

3645 Background: Colorectal cancer (CRC) at early and mid-stages has significantly different prognoses from advanced CRC. Preventing the progression to advanced disease after surgery is crucial for improving survival and reducing healthcare burden. Multiple retrospective studies have shown that Tiaopi Anchang Decoction (TPACD), an oral formula of edible botanical drugs, can reduce recurrence and metastasis risk in CRC when combined with CAPOX. However, the evidence is limited by confounding factors and reporting biases. This study aims to test the hypothesis that CAPOX combined with TPACD can further improve disease-free survival (DFS) in patients with stage III or high-risk stage II CRC. Methods: The study recruited patients from 4 departments of China-Japan Friendship Hospital. It enrolled stage III or high-risk stage II CRC patients undergoing CAPOX and randomly assigned patients in a 1:1 ratio to either the TPACD group (30 mL orally, twice daily) or the placebo group (matched placebo). The trial duration covered 4 chemotherapy cycles, during which CAPOX-induced adverse reactions, quality of life (QoL), safety, and survival outcomes were assessed. The primary endpoint was DFS, while the secondary endpoints included overall survival, the incidence of CAPOX-induced adverse reactions, and QoL score (EORTC QLQ-C30). Kaplan-Meier analysis and Cox proportional hazards regression model were used to evaluate the correlation between CAPOX combined with TPACD and DFS. Results: From December 2022 to September 2024, 496 patients were screened, and 108 were enrolled. The 108 patients were randomly assigned in a 1:1 ratio to the TPACD group or placebo group. 42% were female, the average age was 58 years, and 66% had stage III disease. The interim report has confirmed that TPACD is safe, significantly reduced CAPOX-induced adverse reactions, and improved QoL. Median follow-up time was 28 months, with 17 DFS events (4 TPACD, 13 placebo) and no deaths. Kaplan-Meier analysis estimated 2-year DFS rates of 93.3% for TPACD and 74.7% for placebo. Log-rank testing revealed a statistically significant difference between the two groups ( χ² = 5.329, P = 0.021). CAPOX combined with TPACD significantly reduced the occurrence of DFS events (multivariable hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.073-0.736, P = 0.01) and this effect was not influenced by age, sex, primary tumor site, or TNM stage ( P interaction > 0.05). Conclusions: For patients with stage III and high-risk stage II CRC, TPACD is a well-acceptable complementary therapy. The combination of CAPOX and TPACD not only reduces CAPOX-induced adverse reactions and improves QoL, but also further extends the DFS. Further disclosure of survival data could help optimize adjuvant chemotherapy regimens for CRC. Clinical trial information: ChiCTR2200065759.