Case Report: Durable complete response to dual immune checkpoint blockade and EGFR inhibition in microsatellite-stable metastatic duodenal adenocarcinoma

Background Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with limited treatment options and worse outcomes than colorectal cancer. While immune checkpoint inhibitors (ICIs) show impressive results in mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) tumors, microsatellite-stable (MSS) disease is traditionally considered resistant to immunotherapy. Case We describe a man in his 70s with recurrent duodenal adenocarcinoma who experienced disease progression after multiple systemic therapies, including cetuximab plus FOLFIRI. Molecular profiling by liquid biopsy showed MSS status with low tumor mutational burden (TMB = 1 mutation/Mb). Given the lack of standard alternatives, he was treated with nivolumab, ipilimumab, and cetuximab. Tumor regression was observed within 3 months, followed by a complete radiographic response in October 2022 and a complete metabolic response on PET/CT at 12 months. Immune-related adverse events (irAEs) included grade 2 adrenal insufficiency, vitiligo, and pneumonitis, all of which were manageable. At the latest follow-up in April 2026, the patient had maintained a complete response, approximately 42 months after the first documented radiographic complete response and 27 months after discontinuation of all anticancer therapy. Conclusions This case describes an exceptional durable complete response to dual immune checkpoint blockade combined with an EGFR inhibitor in MSS duodenal adenocarcinoma. Although the relative contribution of each agent and the presence of pharmacologic synergy cannot be determined from a single case, this observation warrants further investigation in prospective trials with MSS SBA.