Optimal neoadjuvant regimens for locally advanced gastric and gastroesophageal junction cancer: a systematic review and bayesian network meta-analysis

BACKGROUND: Large randomized controlled trials (RCTs) have reported data on neoadjuvant therapies for locally advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, no clear recommendation is provided regarding the optimal choice of neoadjuvant regimen. This network meta-analysis (NMA) endeavors to identify the best neoadjuvant therapy for the locally advanced GC and GEJC. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched systematically until September 6, 2024 and update until November 14, 2025. This study encompassed RCTs investigating neoadjuvant treatment for locally advanced GC or GEJC that reported outcomes on overall survival (OS), pathological complete response (pCR), as well as R0 resection rates. Study quality was rated utilizing the Cochrane Risk of Bias Tool 2.0. Bayesian network meta-analysis (BNMA) was conducted through Stata and RStudio for efficacy comparison and ranking of all regimens. RESULTS: 26 RCTs comprising 7,324 patients with GC or GEJC were encompassed. Through the surface under the cumulative ranking curve (SUCRA), DOX ranked highest for OS. FLOT combined with Durvalumab (FLOT_Durvalumab) demonstrated a superior pCR rate, while DOS combined with apatinib (DOS_Apatinib) ranked highest for R0 resection rate. DOX significantly prolonged OS compared with CS (HR = 0.54, 95% CrI: 0.29–0.99), surgery (HR = 0.49, 95% CrI: 0.29–0.84), and XELOX (HR = 0.59, 95% CrI: 0.35–0.99). CONCLUSIONS: DOX appears to be the most effective neoadjuvant treatment for ameliorating OS in patients with GC or GEJC. FLOT_Durvalumab was associated with the highest pCR rate, while DOS_Apatinib appears most effective in achieving R0 resection.