P1.085. Real-World Outcomes of Double Checkpoint Inhibition for MSI-H Gastroesophageal Adenocarcinoma

Abstract

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Gastroesophageal Adenocarcinoma (GEA) is a leading cause of cancer worldwide, with up to 10% of cases harbouring microsatellite instability (MSI-H) characterized by mutations in mismatch-repair proteins. Failure to repair DNA leads to a hypermutated phenotype with neoantigens triggering tumor infiltrating lymphocytes recruitment and activation. The NEONIPIGA trial, showed improved response in MSI-H GEA patients with double immune checkpoint inhibition (ICI) with nivolumab and ipilimumab. Reported pathological complete response rate was 59%. We examined short-term clinical and pathological outcomes of this strategy in a real-world setting. Methods We analyzed prospectively collected data from our single-centre cohort, as part of a broader multicentric international ongoing effort. All adult patients diagnosed with MSI-H gastric or esophagogastric junction (EGJ) adenocarcinoma treated with double ICI followed by resection were included. Descriptive demographics, clinical data and treatment details were collected. Primary outcome was major pathological response (MPR) rate, secondary outcomes were treatment completion and toxicity rates, radiological response, pCR rate, postoperative complications and early oncological outcomes (recurrence and overall survival). Further local, national and international data from partner centres will be pooled and published soon. Results Since November 2020, 28 patients were recruited to our prospective clinical database with the diagnosis of GEA MSI-H. Of these, 6 patients were treated with perioperative double ICI since March 2024 with average age of 73.2 years. Clinical staging ranged between AJCC 8th edition groups IIA-IIIA. All patients completed the 3-month neoadjuvant component of the treatment with no grade 3 adverse events and one event of grade 2 polymyalgia rheumatica. No postsurgical complications were observed, and length of stay was similar to the historical control group. MPR rate was 100% (50% complete response), a statistically significant difference when compared to the 8 patients that received any other form of systemic therapy. All but one patient resumed postoperative immunotherapy. All patients are alive and disease free at a median follow up of 8 months. Conclusion The implementation of double ICI for MSI-H gastric or EGJ adenocarcinoma is feasible and yields comparable efficacy to that reported within the landmark clinical trial with low rates of serious adverse events. Other ICIs are approved for esophagogastric cancer but real-world data on their use is lacking. Further studies are needed focusing on determinants of response with the goal of maximizing the proportion of complete responders. Our findings further call for the reassessment of the role of surgery and the implementation of organ preservation strategies.