S1011 Feasibility of Non-Operative Management Following Neoadjuvant Immune Checkpoint Inhibitors in Resectable dMMR/MSI-H Gastroesophageal Adenocarcinoma

Introduction: Neoadjuvant immune checkpoint inhibitors (nICIs) have demonstrated high response rates in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) gastroesophageal adenocarcinoma (GEA). The NEONIPIGA and INFINITY trials reported promising rates of pathological complete response (pCR), with early data suggesting non-operative management (NOM) may be feasible. We evaluated real-world outcomes of nICIs in resectable dMMR/MSI-H GEA, with emphasis on the potential for NOM. Methods: We conducted a retrospective cohort study across multiple tertiary centers, identifying patients with histologically confirmed, resectable dMMR/MSI-H GEA treated with nICIs between April 1, 2017, and February 28, 2025. Patients with metastatic disease or incomplete records were excluded. Patients were treated with nICIs, followed either by surgery or NOM. Clinical complete response (cCR) was defined as absence of residual tumor on imaging and endoscopic evaluation. Primary outcomes included cCR, pathological complete response (pCR), and metastasis-free survival (MFS). Secondary outcomes included radiological complete response (rCR), and immune-related adverse events (irAEs). Results: A total of 26 patients were included (median age 70 years; 61.5% men). Eight patients (30.8%) underwent surgical resection after nICIs, with 5 of 8 (62.5%) achieving pCR. Eighteen patients (69.2%) underwent or are undergoing NOM. Among 18 evaluable NOM patients, 10 of 14 evaluable patients (71.4%) achieved cCR, and 12 of 18 (66.7%) achieved rCR. Seventeen out of the 18 patients in the non-operative management cohort (94.4%) are alive and metastasis-free, with a median metastasis-free survival of 13.5 months (range: 4.1-81.8). Immune-related adverse events occurred in nine patients (34.6%), with no grade ≥3 toxicities. Conclusion: This study highlights the potential of nICIs to induce high response rates in resectable dMMR/MSI-H GEA, with many patients achieving durable clinical complete responses without surgery. These findings support the feasibility of a non-operative, organ-preserving approach in selected patients and warrant further investigation in prospective studies.