Precision Oncology in Duodenal Adenocarcinoma: A Case of Metastatic BRAF V600E-mutant Disease Treated with Encorafenib, Cetuximab, Chemotherapy, and Immunotherapy

Abstract Duodenal adenocarcinoma is a rare malignancy that is often managed with protocols extrapolated from colorectal cancer (CRC) due to limited disease-specific evidence. We present the case of a 28-year-old female with metastatic BRAF V600E-mutant, human epidermal growth factor receptor 2 (HER2)-positive, and programmed death-ligand 1 (PD)-positive duodenal adenocarcinoma. After progression on chemotherapy, anti-PD-1 immunotherapy, and anti-HER2 targeted therapy, she received a combination of encorafenib, cetuximab, folinic acid, 5-fluorouracil, and irinotecan, and atezolizumab, which resulted in marked regression of hepatic, lymphatic, and ovarian metastases. This case illustrates the potential value of comprehensive genomic profiling and suggests that CRC-derived targeted therapies may be considered in patients with small bowel adenocarcinoma with similar molecular alterations.