Neoadjuvant Dual Immunotherapy in T4 Locally Advanced Deficient Mismatch Repair Gastric or Esophagogastric Junction (EGJ) Adenocarcinoma.

Although combining programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors in neoadjuvant therapy is effective for deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) gastric or esophagogastric junction (EGJ) adenocarcinoma, few T4 stage patients have been studied. The effectiveness and safety of this dual immunotherapy for T4 locally advanced dMMR/MSI-H gastric/EGJ adenocarcinoma is largely unknown. Patients with T4 locally advanced dMMR/MSI-H gastric/EGJ adenocarcinoma treated with dual immune checkpoint inhibitors as neoadjuvant therapy were identified from a prospectively maintained gastric/EGJ adenocarcinoma database. The primary endpoint was the pathological complete response (pCR) rate. Twenty-three patients were included in this study. Of these, 22 (95.7%) completed dual immunotherapy before surgery, while one missed a dose due to immune-related hypophysitis. Sixteen patients (69.6%) underwent surgery, achieving a 100% R0 resection rate. The pCR rate was 81.3% (95% confidence interval (CI): 57.0%-93.4%) and the major pathological response (MPR) rate was 93.8%. Seven patients did not have surgery; five of them, with complete clinical response, opted for a "watch-and-wait" strategy. The event-free survival rate was 95.5% at a median follow-up of 22.1 months, with manageable adverse events. Dual immunotherapy shows promise for T4 locally advanced dMMR/MSI-H gastric/EGJ adenocarcinoma, and the "watch-and-wait" strategy deserves further study in dMMR/MSI-H cases. Larger studies are needed to confirm these results and optimize treatment.