SAT-090 - Response to cabozantinib in a patient with a non-functional grade 3 pancreatic neuroendocrine tumor after multiple prior lines of systemic therapy

ABSTRACT
Well-differentiated grade 3 pancreatic neuroendocrine tumors (pNETs) represent a therapeutic challenge due to their aggressive behavior and the lack of a standard of care following progression on conventional therapies. Cabozantinib, a multi-tyrosine kinase inhibitor targeting VEGFR2, MET, AXL, and RET, has emerged as a promising treatment option in neuroendocrine tumors with disease progression after multiple lines of systemic therapy.

Case Presentation:
A 56-year-old man with a non-functional grade 3 pancreatic neuroendocrine tumor (pNET; Ki-67 index 25%), stage IV (hepatic metastases), presented with tumor progression after multiple lines of treatment, including cytoreductive surgery, ablation of hepatic metastases combined with somatostatin analogs, chemotherapy with capecitabine–temozolomide (CAPTEM), and peptide receptor radionuclide therapy (¹⁷⁷Lu-DOTATATE).

Following progression on radionuclide therapy, new hypermetabolic lesions were identified on FDG-PET. Image-guided biopsy of these lesions confirmed pNET without changes in the Ki-67 index. Systemic treatment with cabozantinib (60 mg/day) was subsequently initiated.

Results:
Treatment with cabozantinib achieved an early partial response (at 3 months), with a maximum 40% reduction in target lesions observed at eight months from treatment initiation. The drug was well tolerated, with adverse events including hypertension, dysgeusia, transient elevation of transaminases, and subclinical hypothyroidism, without impairment in quality of life (ECOG performance status 1).

Conclusion:
This case provides real-world evidence supporting the efficacy of cabozantinib in heavily pretreated patients with grade 3 pancreatic neuroendocrine tumors (pNETs), with an acceptable safety profile. Patients with grade 3 neuroendocrine tumors currently have limited therapeutic options; therefore, the availability of treatments that improve progression-free survival in this setting is of particular importance.

Keywords: Pancreatic neuroendocrine tumor; grade 3; cabozantinib; radionuclide therapy; therapeutic resistance.

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