Neoadjuvant tislelizumab plus oxaliplatin and S-1 for locally advanced Siewert type II esophagogastric junction adenocarcinoma: A prospective multicenter phase II study.

Abstract

4091 Background: Adenocarcinoma of the esophagogastric junction (AEG) is a malignant tumor with high morbidity and mortality globally. Among subtypes, Siewert type Ⅱ AEG remains a clinical challenge owing to its unique anatomical location and distinct clinicopathological features. This study aimed to evaluate the efficacy and safety of Tislelizumab in combination with oxaliplatin and S-1 as neoadjuvant therapy for patients with locally advanced Siewert type Ⅱ AEG. Methods: This is a prospective, multicenter clinical trial. Eligible patients were aged 19-75 years with pathologically confirmed Siewert type II adenocarcinoma of the esophagogastric junction, clinical stage T2-4N0-3M0, ECOG performance status 0-1, and adequate major organ function. All patients received 3 cycles of neoadjuvant therapy consisting of: tislelizumab (200 mg, D1, Q3W), oxaliplatin (130 mg/m², D1, Q3W), and S-1 (40-60mg based on BSA, po, bid, D1-14, Q3W). Following efficacy evaluation, patients underwent resection of the esophagogastric junction adenocarcinoma 4-8 weeks after completion of neoadjuvant therapy. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include major pathologic response (MPR), objective response rate, R0 resection rate, overall survival (OS), disease-free survival (DFS), and safety. Results: As of June 2025, a total of 40 patients were enrolled in this study. The median age was 66 years (range, 37-76), 87.5% were male, and 92.5% had an ECOG performance status of 0. Among them, 87.5% (n = 35) of the patients completed 3 cycles of neoadjuvant therapy. The remaining 5 cases completed 1 (n = 1, due to grade≥3 TRAEs), 2 (n = 2, due to grade≥3 TRAEs and patient decision, respectively), and 4 (n = 2, patient decision) cycles of treatment. All patients underwent resection of the esophagogastric junction adenocarcinoma. The R0 resection rate was 97.5% (39/40), with no patients requiring re-operation or experiencing perioperative mortality. The pathologic complete response (pCR) rate was 25% (10/40). The primary tumor pCR rate reached 30% (12/40), and the major pathologic response (MPR) rate was 37.5% (15/40). Treatment-related adverse events (TRAEs) of any grade occurred in 95% (38/40) of patients, with grade ≥3 TRAEs observed in 15% (6/40). Conclusions: Neoadjuvant therapy with Tislelizumab in combination with oxaliplatin and S-1for locally advanced Siewert type Ⅱ esophagogastric junction adenocarcinoma yields a favorable pathological complete response (pCR) rate and shows a good safety profile. Clinical trial information: ChiCTR2300075638.