[Comment] Rethinking treatment sequence in advanced gastroenteropancreatic neuroendocrine tumours

Rethinking treatment sequence in advanced gastroenteropancreatic neuroendocrine tumours Affiliations & Notes Pancreas and Transplant Surgery Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, 20132, Italy Article Info Publication History: Published July 2, 2026 DOI: 10.1016/S0140-6736(26)01080-9 External LinkAlso available on ScienceDirect External Link Copyright: © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. Linked Articles Treatment sequencing in advanced gastroenteropancreatic neuroendocrine tumours (GEP-NETs) remains a major unmet clinical need.1 Although somatostatin receptor-positive, well differentiated GEP-NETs often follow a somewhat indolent course, disease progression eventually requires treatment decisions that balance tumour control, toxicity, quality of life, and the preservation of future therapeutic options. References 1. Pavel, M ∙ Öberg, K ∙ Falconi, M ∙ et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol. 2020; 31:844-860 2. Strosberg, J ∙ El-Haddad, G ∙ Wolin, E ∙ et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors N Engl J Med. 2017; 376:125-135 3. Singh, S ∙ Halperin, D ∙ Myrehaug, S ∙ et al., NETTER-2 Trial Investigators [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study Lancet. 2024; 403:2807-2817 4. Walter, T ∙ Jann, H ∙ Ansquer, C ∙ et al. [177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial Lancet. 2026; published online July 2. https://doi.org/10.1016/S0140-6736(26)00604-5 5. Yao, JC ∙ Shah, MH ∙ Ito, T ∙ et al. Everolimus for advanced pancreatic neuroendocrine tumors N Engl J Med. 2011; 364:514-523 6. Yao, JC ∙ Fazio, N ∙ Singh, S ∙ et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study Lancet. 2016; 387:968-977 7. Strosberg, JR ∙ Caplin, ME ∙ Kunz, PL ∙ et al. 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial Lancet Oncol. 2021; 22:1752-1763 8. Pusceddu, S ∙ Prinzi, N ∙ Tafuto, S ∙ et al. Association of upfront peptide receptor radionuclide therapy with progression-free survival among patients with enteropancreatic neuroendocrine tumors JAMA Netw Open. 2022; 5, e220290