A Rare BRAF Fusion in Advanced Rectal Cancer Treated with Anti-Epidermal Growth Factor Receptor Therapy

Recently, v-raf murine sarcoma viral oncogene homologue B (BRAF) fusions have been identified in multiple cancer types using comprehensive genomic profiling (CGP) assays. BRAF fusions are extremely rare, occurring in <0.5% of patients with metastatic colorectal cancer (mCRC). Until now, there is no standard treatment for mCRC with BRAF fusions. Here, we report a recurrent colorectal cancer case that harbored an EXOC4-BRAF fusion. A 40-year-old female patient with a 2-year history of type 2 diabetes was diagnosed with pathologically confirmed stage IV rectal adenocarcinoma with liver metastasis. She underwent R0 resection after neoadjuvant therapy; however, her disease recurred at multiple metastatic sites (lymph nodes, ovary, and peritoneal gland). A rectal cancer surgical specimen was submitted for CGP (Foundation One) to identify potential targets to develop treatment strategies. An EXOC4-BRAF fusion was identified, and she achieved partial response to FOLFOX + panitumumab which is a fully human antibody directed against epidermal growth factor receptor. No EXOC4-BRAF fusions in colorectal cancer cases have been reported to date. Further studies investigating molecular mechanisms and novel targeted therapy approaches are required.