Perioperative Nivolumab Combined with Neoadjuvant Chemotherapy in Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

Objective: The exact role of nivolumab in the perioperative systemic treatment of locally advanced-gastric/gastroesophageal junction (LA-G/GEJ) adenocarcinoma remains unclear.This study aimed to evaluate the real-world effectiveness and safety of perioperative nivolumab in patients with LA-G/GEJ adenocarcinoma. Material and Methods:Clinical and pathological data were retrospectively collected for previously untreated patients with human epidermal growth factor receptor 2-negative, clinical stage T2-4bN0-3M0 (stage II-III) G/GEJ adenocarcinoma, either microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) or microsatellite stable (MSS)/proficient MMR (pMMR) with a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of ≥5, who received perioperative nivolumab in combination with chemotherapy or ipilimumab between January 2021 and April 2025.Kaplan-Meier survival analysis was used to estimate disease-free survival (DFS) and overall survival (OS).Results: Fifteen eligible patients were identified among 134 with stage II-III G/GEJ adenocarcinoma.Seven patients (46.7%) were classified as MSI-H/ dMMR, and 11 patients (73.3%) had a PD-L1 CPS of ≥5.The median numbers of immunotherapy and chemotherapy cycles prior to surgery were 6 (range, 3-8) and 8 (range, 1-8), respectively.Objective response and disease control rates were 60% and 100%, respectively.All patients underwent surgical resection, and the R0 resection rate was 93.3%.Pathological complete response and major pathological response rates were both 71.4% in the MSI-H/dMMR subgroup, compared to 25% and 37.5%, respectively, in MSS/pMMR patients with a PD-L1 CPS ≥5.During follow-up [median 17.0 months (95% confidence interval: 13.0-20.9)],four patients experienced tumor recurrence, and three died.All cases of disease recurrence and death occurred in the MSS/pMMR subgroup, with 18 months DFS and OS rates of 35.7% and 47.6%, respectively. Conclusion:For the treatment of LA-G/GEJ adenocarcinoma, perioperative nivolumab combined with total neoadjuvant chemotherapy might be effective for both MSI-H/dMMR patients and MSS/pMMR patients with a PD-L1 CPS of ≥5, and have an acceptable safety profile.