Achieving Stable Disease in an Adult with Malignant Gastrointestinal Tumor following Cabozantinib Treatment: Case Report.

Introduction: Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare and aggressive neoplasm that is characterized by EWSR1 rearrangements. Most patients present with metastatic disease. There are no established treatment guidelines, and systemic therapy options remain poorly defined. Case Presentation: A woman in her late 30s presented initially with right upper quadrant pain and bloating. Endoscopic biopsy of a duodenal mass revealed a SOX10-positive malignant neoplasm. Molecular testing identified an EWSR1:CREB1 fusion, confirming GNET. Initial treatment with ipilimumab and nivolumab resulted in disease progression. Subsequent therapies included a selective interleukin-2 agonist clinical trial, nivolumab/relatlimab, and temozolomide, all associated with continued progression. Cabozantinib was initiated after further radiographic progression. Follow-up imaging demonstrated tumor regression, and the patient maintained stable disease for 15 months before mild progression. Conclusion: Metastatic GNET has a poor prognosis and lacks standardized systemic therapy. This case demonstrates durable disease stabilization with cabozantinib after progression on immunotherapy and chemotherapy. Tyrosine kinase inhibition may represent a promising therapeutic strategy in GNET and warrants further investigation.