Adjuvant oxaliplatin plus S-1 versus docetaxel plus S-1 for stage III gastric cancer after D2 gastrectomy (DRAGON-Adjuvant): A multicenter, open-label, phase 3, randomized, non-inferiority study.

TPS4249 Background: Adjuvant therapy is the standard treatment for stage II-III gastric cancer patients after radical D2 gastrectomy. Neoadjuvant therapy has been demonstrated as an effective strategy for resectable gastric cancer patients, while less than 2% of patients received such treatment in China. Therefore, adjuvant chemotherapy following radical resection is still widely used in current clinical practices. For stage III gastric cancer patients, oxaliplatin or docetaxel combined with oral fluoropyrimidine as adjuvant regimens are recommended by clinical guidelines. Although historical data show comparable efficacy between these regimens, direct comparisons are not feasible due to differences in study design, enrolled populations, and treatment cycles. Regimen selection is mainly based on clinical experience, as high-level evidence is still lacking. Currently, minimal residual disease (MRD) detection based on ctDNA testing can indicate patient prognosis and adjuvant therapy selection in colorectal cancer. The role of ctDNA-based MRD detection in adjuvant therapy of gastric cancer is still under investigation. This study aims to compare the efficacy and safety of oxaliplatin plus S-1 (SOX) versus docetaxel plus S-1 (DS) as adjuvant therapy for stage III gastric cancer, and to explore the role of MRD in adjuvant setting of gastric cancer. Methods: DRAGON-Adjuvant (NCT07366528) is a prospective, open-label, multicenter, randomized, non-inferiority study in patients aged from 18 to 80 years who are histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction, with pathological staging at AJCC stage IIIA to IIIC after standard D2 gastrectomy and R0 resection. Patients had no prior neoadjuvant therapy. Eligible patients will be randomized and assigned into experiment group (SOX, n = 193) and control group (DS, n = 194), respectively. Experiment group patients will be treated with eight 3-week cycles of intravenous oxaliplatin (130mg/m 2 on day 1 for each cycle) with orally S-1 on days 1 to 14 of a 3-week cycle. Control group patients will be treated with S-1 on days 1 to 14 of a 3-week cycle (C1), then intravenous infusion of docetaxel (40mg/m 2 ) on day 1 of each cycle and S-1 on days 1 to 14 of a 3-week cycle (C2 to 7), then S-1 continued on days 1 to 28 of 6-week cycles for up to 1 year. S-1 dose is dependent on body surface area. The primary objective is to assess that 3-year disease-free survival rate of SOX group is not inferior to DS group. Secondary objectives are to compare the 5-year overall survival rate, safety profiles, and recurrence sites in two groups. Exploratory objective is to assess the correlation of MRD with treatment efficacy and patient prognosis. As of January 2026, the DRAGON-Adjuvant is recruiting patients at 5 sites in China. Clinical trial information: NCT07366528 .