Treatment Landscape for Advanced NETs

EP: 1.Understanding Neuroendocrine Tumors in Practice

Now Viewing

EP: 2.Treatment Landscape for Advanced NETs

EP: 3.Evolving Needs in Advanced NET Care

EP: 4.Cabozantinib in Context – CABINET Rationale and Trial Design

EP: 5.Interpreting the Clinical Efficacy of Cabozantinib in NETs

EP: 6.Safety Insights From the CABINET Trial

EP: 7.Integrating Cabozantinib Into the NET Treatment Landscape

EP: 8.Managing NET Patients on Cabozantinib – Practical Insights

EP: 9.Looking Ahead: The Future of Care for NETs

Over the last 2 decades, the management of advanced neuroendocrine tumors (NETs) has significantly progressed, though some foundational practices remain unchanged. For localized or symptomatic disease, surgical resection continues to be a standard approach, especially for small, low-grade pancreatic tumors under 2 cm, which can often be safely monitored instead of removed. In advanced cases, the majority of tumors express somatostatin receptors, making somatostatin analogues (SSAs) such as octreotide and lanreotide the primary first-line treatments. Clinical trials have shown these agents not only control symptoms but also delay tumor progression. While many patients respond well for extended periods—some even decades—most experience disease progression within 2 to 4 years of initiating therapy.

Following progression on SSAs, treatment choices vary depending on tumor origin. Small bowel NETs are commonly treated with peptide receptor radionuclide therapy (PRRT) using lutetium-177, particularly when surgical or regional therapies are no longer viable. Pancreatic NETs offer more therapeutic options, including PRRT, chemotherapy with capecitabine-temozolomide, and targeted therapies like everolimus. Though everolimus can slow tumor growth, it is less effective for carcinoid syndrome. Newer treatments, such as alpha particle therapies and tyrosine kinase inhibitors like cabozantinib, are expanding options, especially for small bowel NETs, which have historically had fewer alternatives. Each therapy presents its own adverse effects and levels of efficacy, reinforcing the need for personalized treatment strategies.

The effectiveness and adverse effects of SSAs can vary greatly between individuals. On average, clinical trials show tumor control ranging from 18 to 35 months, with pancreatic NETs typically responding for shorter durations. A predictive tool, the TRASGU calculator, can help estimate progression risk for newly diagnosed patients based on clinical and lab data. In some low-grade, low-volume metastatic cases, active surveillance without immediate treatment is appropriate. Adverse effects of SSAs include monthly injection inconvenience and gastrointestinal issues such as steatorrhea, linked to pancreatic insufficiency. These are usually manageable, though rising costs of supportive medications pose challenges.