Clinical Perspectives on the Treatment of Neuroendocrine Tumors - Episode 7
Panelists discuss how cabozantinib approval helps fill treatment gaps for patients who have exhausted standard therapies like somatostatin analogs, peptide receptor radionuclide therapy (PRRT), and everolimus, providing a new option for healthy patients seeking additional treatment lines in this indolent but progressive disease.
Historical Development of Targeted Therapies
The RADIANT trial series revolutionized neuroendocrine tumor (NET) treatment by establishing targeted therapy efficacy. RADIANT-1 provided proof of concept at MD Anderson, leading to RADIANT-2 (focused on carcinoid tumors) and RADIANT-3 (pancreatic NETs). RADIANT-3, despite opening after RADIANT-2, completed first and was published in the New England Journal of Medicine in February 2011, providing a new standard of care for pancreatic NETs.
Remarkably, the same NEJM issue featured back-to-back papers on NET treatment, with sunitinib data appearing alongside everolimus results. This unprecedented publication of 2 practice-changing trials established sunitinib for pancreatic NETs and everolimus initially for pancreatic tumors, though RADIANT-2 suggested broader activity. RADIANT-4 later confirmed everolimus efficacy in nonfunctional NETs, extending treatment options to thoracic primaries by 2017.
The lutetium-177 dotatate (NETTER-1) trial matured around the same time frame, introducing PRRT for advanced gastroenteropancreatic NETs. Concurrently, capecitabine-temozolomide data emerged showing significant response rates in pancreatic NETs, with over 50% achieving meaningful tumor reduction. This combination enabled neoadjuvant approaches for surgical candidates and formed the basis for ongoing adjuvant studies in resected pancreatic NETs.