Abstract
BRAF mutations, particularly BRAF V600E, are rare but clinically significant molecular alterations in intrahepatic cholangiocarcinoma (IHCC), often linked to aggressive disease and poor prognosis. While targeted therapies have shown efficacy in BRAF-mutant colorectal cancer, their role in IHCC remains uncertain. This report describes the case of a 59-year-old woman with advanced BRAF V600E-mutated IHCC (cT3N3M1c, stage IVc) treated with encorafenib, binimetinib, and cetuximab. The BRAF V600E mutation was identified through next-generation sequencing. Initially, the patient was given gemcitabine, cisplatin, and durvalumab as first-line chemotherapy; however, her metastatic lesions progressed rapidly within one month. Due to the lack of response, second-line treatment with encorafenib, binimetinib, and cetuximab was started, resulting in a favorable initial response. Unfortunately, the disease progressed five months after initiating this regimen. This case highlights the potential benefit of combined BRAF/MEK/EGFR inhibition in BRAF V600E-mutated IHCC and underscores the need for further research to optimize treatment strategies for this patient population.