Clinical Research Directory

Real World Positioning of Tyrosine Kinase Inhibitors (TKIs) Within Systemic Treatment Strategies for Advanced Neuroendocrine Tumors (NETs)

Well differentiated neuroendocrine tumors (NETs) are rare and heterogeneous malignancies that frequently evolve toward advanced or metastatic disease, requiring long-term systemic treatment strategies delivered over multiple lines. Their management is complex and influenced by tumor-related factors-including primary site and grade-as well as disease burden, functional status, patient comorbidities, and access to available therapeutic options. As a result, real-world treatment pathways in advanced NETs are highly diverse. In recent years, the systemic treatment landscape of advanced NETs has expanded beyond somatostatin analogues (SSA), peptide receptor radionuclide therapy (PRRT), and chemotherapy to include targeted therapies. Among these, multitarget tyrosine kinase inhibitors (TKIs) targeting tumor angiogenesis have progressively been incorporated into clinical practice. Their use varies according to tumor subtype, disease dynamics, prior treatments, and patient-related considerations, reflecting the absence of standardized sequencing algorithms. In routine clinical practice, the choice and sequencing of TKIs are driven by individualized clinical decision-making rather than predefined treatment pathways. Their positioning within systemic treatment strategies is influenced by anticipated benefit, tolerability, prior toxicities, and practical constraints such as regulatory indications, access, and reimbursement conditions, which differ by tumor origin. Consequently, the real-world positioning of TKIs within treatment sequences remains insufficiently characterized at a national level. "SEQUENCE-NET" is an ambispective observational study designed to prospectively document how TKIs are integrated into systemic treatment strategies for advanced pancreatic and extra-pancreatic NETs in routine clinical practice within the ENDOCAN-RENATEN network.