Evaluation of the safety and efficacy of sintilimab combined with chemotherapy as neoadjuvant therapy for locally advanced gastric/gastroesophageal junction adenocarcinoma: Short-term results of a multicenter phase II study.

Abstract

e16117 Background: Perioperative chemotherapy combined with gastrectomy and lymphadenectomy is the standard treatment for resectable locally advanced gastric/gastroesophageal junction adenocarcinoma (LAGC). Despite clinical trials confirming survival benefits of neoadjuvant chemotherapy (NACT) in resectable LAGC, many patients remain unresponsive, with low pathological complete response (pCR) rates. Sintilimab, a fully human, highly selective anti-PD-1 monoclonal antibody, blocks PD-1 interactions with PD-L1/PD-L2, eliciting a robust antitumor response. Combining sintilimab with NACT and radical resection may improve tumor downstaging and reduce distant recurrence risks. Methods: This study assessed the feasibility, efficacy, and safety of sintilimab combined with chemotherapy as neoadjuvant therapy for LAGC. Patients from three Chinese clinical centers with stage II (cT3-4N0M0 or cT1-3N1-3M0) or stage III (cT3-4aN1-3M0) LAGC were enrolled. Patients received sintilimab (200 mg, iv.gtt, Day 1, every 3 weeks) with XELOX chemotherapy (capecitabine: 1000 mg/m², oral, twice daily, Days 1-14, every 3 weeks; oxaliplatin: 130 mg/m², iv.gtt, Day 1, every 3 weeks) for three cycles. Preoperative imaging 3-4 weeks post-treatment evaluated efficacy and radical D2 resection eligibility. The primary endpoint was the pCR rate, with secondary endpoints including the major pathological response (MPR) rate, R0 resection rate, objective response rate (ORR), and disease control rate (DCR). Results: Between June 2023 and January 2025, 26 patients (10 gastric cancer, 13 gastroesophageal junction adenocarcinoma) were enrolled. As of January 20, 2025, 23 patients underwent radical surgery with an R0 resection rate of 100%. The pCR rate was 30.4% (7/23), and the MPR rate was 47.8% (11/23). ORR and DCR were 60.9% and 91.3%, respectively. Immune-related adverse events (irAEs) occurred in 4 patients (13.0%), including liver dysfunction (grade 3 and grade 1), hypothyroidism (grade 1), and dermatitis (grade 1). One patient experienced an anastomotic hemorrhage (4.3%), with no cases of anastomotic leakage or treatment-related death. Conclusions: The addition of sintilimab to neoadjuvant chemotherapy for LAGC, followed by radical surgery, demonstrated promising efficacy and a favorable safety profile. These results highlight a potential new strategy for neoadjuvant treatment of LAGC, warranting further validation through large-scale randomized clinical trials.