{"entity":{"id":"paper-netter-2-lancet-2024","kind":"paper","name":"NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours","aka":[],"tldr":"Using the radioactive drug lutetium dotatate as the first treatment for faster-growing neuroendocrine tumours, rather than saving it for later, nearly tripled the time without progression compared with high-dose octreotide.","summary":"Open-label phase 3 trial of 226 patients with newly diagnosed, somatostatin-receptor-positive grade 2-3 (Ki-67 10-55%) advanced gastroenteropancreatic neuroendocrine tumours randomised 2:1 to four cycles of 177Lu-dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR (60 mg). Primary endpoint was PFS by blinded review.\n\nMedian PFS was 22.8 vs 8.5 months (HR 0.28) with an objective response rate of 43% vs 9%. Following NETTER-1 (which established lutetium dotatate in progressive midgut tumours), it moved radioligand therapy to the first line for higher-grade disease, where somatostatin analogues alone are weak.","asOf":"2026-09-08","links":[{"label":"PubMed search: NETTER-2 Lancet 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet"},{"label":"ClinicalTrials.gov NCT03972488","url":"https://clinicaltrials.gov/study/NCT03972488"}],"tags":[],"related":[],"cancers":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","pet-ct"],"targets":["sstr2"],"drugs":["lutathera"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":["theranostics","pfs","orr","first-line","dosimetry"],"trials":[],"people":["oh-do-youn"],"bottlenecks":["b-rare-cancers","b-global-access","b-trial-design"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)00701-3","pmid":"38851203","authors":"Singh S, Halperin D, Myrehaug S, et al.","paperType":"rct","findings":["Median PFS 22.8 vs 8.5 months; HR 0.28 (95% CI 0.18-0.42).","Objective response 43.0% vs 9.3%.","Benefit consistent in grade 2 and grade 3 tumours and in pancreatic and small-bowel primaries.","Grade 3 or higher adverse events about 35% vs 28%; no cases of treatment-related myelodysplasia or leukaemia at the primary analysis.","Overall survival data immature; crossover to lutetium dotatate was permitted at progression."],"whatItMeans":"Patients newly diagnosed with an advanced grade 2 or 3 neuroendocrine tumour of the gut or pancreas that shows somatostatin receptors on imaging can now receive lutetium dotatate as their first treatment, gaining more than a year of additional disease control and a much higher chance of tumour shrinkage. It does not settle whether radioligand therapy is better than other first-line options such as capecitabine-temozolomide or everolimus, and long-term marrow safety with earlier use needs surveillance.","caveats":["Comparator was high-dose octreotide, which has limited anti-proliferative activity in grade 2-3 tumours.","Overall survival not yet shown; crossover will make it hard to demonstrate.","Long-term risks of earlier radioligand exposure (marrow, kidney, secondary leukaemia) require follow-up.","Requires somatostatin-receptor PET and nuclear medicine capacity; grade 3 tumours with Ki-67 above 55% were excluded."],"changedPractice":true,"participants":226},"route":"/key-papers/paper-netter-2-lancet-2024/","neighbours":{"cancer":[{"id":"grade-3-net","kind":"cancer","name":"Grade 3 well-differentiated neuroendocrine tumour","route":"/cancers/grade-3-net/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"pancreatic-net","kind":"cancer","name":"Pancreatic neuroendocrine tumours","route":"/cancers/pancreatic-net/"},{"id":"small-intestinal-net","kind":"cancer","name":"Small intestinal neuroendocrine tumours","route":"/cancers/small-intestinal-net/"}],"technology":[{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"}],"target":[{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"drug":[{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","route":"/drugs/lutathera/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"term":[{"id":"dosimetry","kind":"term","name":"Dosimetry","route":"/terms/dosimetry/"},{"id":"first-line","kind":"term","name":"Lines of therapy","route":"/terms/first-line/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"theranostics","kind":"term","name":"Theranostics","route":"/terms/theranostics/"}],"person":[{"id":"oh-do-youn","kind":"person","name":"Do-Youn Oh","route":"/people/oh-do-youn/"},{"id":"jonathan-strosberg","kind":"person","name":"Jonathan R. Strosberg","route":"/people/jonathan-strosberg/"},{"id":"simron-singh","kind":"person","name":"Simron Singh","route":"/people/simron-singh/"}],"bottleneck":[{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}