Yiqi Huayu Jiedu decoction enhances pathological response in neoadjuvant chemotherapy-treated gastric cancer patients: A prospective, randomized controlled trial.

[BACKGROUND] While neoadjuvant chemotherapy (NAC) shows suboptimal pathological responses in advanced gastric cancer (GC), Yiqi Huayu Jiedu decoction (YHJD) demonstrates potential as a synergistic agent.

[METHODS] This study represents an interim analysis of a prospective, double-arm, single-center, randomized controlled clinical trial (ChiCTR2300072742) conducted at Jiangsu Provincial Hospital of Traditional Chinese Medicine. A total of 122 patients with locally advanced GC were enrolled between June 2023 and December 2024. The study aimed to evaluate the efficacy and safety of YHJD in enhancing the neoadjuvant FLOT regimen. The primary endpoint was tumor pathological regression (TRG).

[RESULTS] The YHJD group demonstrated superior pathological responses (TRG 1-3: YHJD group vs CON group: 44/68 [68.8%] vs 29/58 [50.0%], p = 0.043) while maintaining a safety profile comparable to chemotherapy alone. Gut microbiota analysis revealed that YHJD significantly reduced the abundance of Lactobacillus salivarius (L.salivarius) during NAC, with lower levels correlating with improved treatment response. Notably, depletion of intratumoral L.salivarius in the YHJD paralleled enhanced NAC efficacy. Further analysis revealed that enrichment of L. salivarius was associated with immunosuppressive microenvironment, it showed positive correlations with T regulatory cells (Tregs; r = 0.512, p < 0.0001) and M2 macrophages (r = 0.411, p = 0.002).

[CONCLUSIONS] YHJD enhanced the pathological response rates in GC patients receiving FLOT-based NAC, possibly through modulation of the immuno-oncology-microbiome axis, potentially by downregulating L. salivarius-mediated immunosuppression.