Inadequate Response and Second-Line Treatment of NETS

The discussion focused on second-line management of neuroendocrine tumors (NETs) following progression on somatostatin analogs (SSAs). Dr. Chauhan highlighted that the expanding range of therapies makes progression a “good problem to have,” though treatment decisions remain site-specific and biology-driven. Peptide receptor radionuclide therapy (PRRT) is now widely considered a preferred second-line option for SSTR-positive tumors, supported by NETTER-1 and NETTER-2 trials, offering disease control and improved quality of life with limited dosing and infusions.

For pancreatic NETs, additional options include mTOR inhibitors (everolimus), tyrosine kinase inhibitors (sunitinib, cabozantinib), and chemotherapy with capecitabine-temozolomide, particularly for higher-grade tumors. Clinical trials and emerging therapies, including alpha/beta PRRT are also encouraged. For extra-pancreatic NETs, treatment options are more limited but still include PRRT, capecitabine-temozolomide, and chemotherapy in select aggressive cases. Overall, the panel emphasized the importance of personalizing therapy based on tumor site, grade, receptor status, and patient-specific factors, reflecting the growing complexity and opportunity in NET management.