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Clinical Perspectives on the Treatment of Neuroendocrine Tumors - Episode 7

Cabozantinib Approval for NET Treatment

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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.

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    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.

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