# NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours

Source: https://nuclide.cc/key-papers/paper-netter-2-lancet-2024/  
Nuclide record `paper-netter-2-lancet-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

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.

Median 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: The Lancet
- Year: 2024
- DOI: 10.1016/S0140-6736(24)00701-3
- Authors: Singh S, Halperin D, Myrehaug S, et al.
- 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.
- What it means: 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.

## Sources

- PubMed search: NETTER-2 Lancet 2024: https://pubmed.ncbi.nlm.nih.gov/?term=NETTER-2+lutetium+dotatate+first-line+Singh+Lancet
- ClinicalTrials.gov NCT03972488: https://clinicaltrials.gov/study/NCT03972488

## Connected records

- isotopes: [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)
- indications: [Grade 3 well-differentiated neuroendocrine tumour](https://nuclide.cc/indications/grade-3-net/), [Neuroendocrine tumours](https://nuclide.cc/indications/neuroendocrine/), [Pancreatic neuroendocrine tumours](https://nuclide.cc/indications/pancreatic-net/), [Small intestinal neuroendocrine tumours](https://nuclide.cc/indications/small-intestinal-net/)
- technologies: [PET/CT](https://nuclide.cc/technologies/pet-ct/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/)
- targets: [Somatostatin receptor 2](https://nuclide.cc/targets/sstr2/)
- drugs: [Lutetium-177 dotatate](https://nuclide.cc/drugs/lutathera/)
- companies: [Novartis](https://nuclide.cc/companies/novartis/)
- terms: [Dosimetry](https://nuclide.cc/terms/dosimetry/), [Theranostics](https://nuclide.cc/terms/theranostics/)
- journals: [The Lancet](https://nuclide.cc/journals/lancet/)
- people: [Jonathan R. Strosberg](https://nuclide.cc/people/jonathan-strosberg/), [Simron Singh](https://nuclide.cc/people/simron-singh/)
- fronts: [Radioligand therapy](https://nuclide.cc/fronts/f-radioligand-therapy/)
- roadmaps: [SSTR theranostics roadmap: octreotide scintigraphy → 68Ga-DOTATATE → 177Lu-DOTATATE → alpha](https://nuclide.cc/roadmaps/sstr-theranostics-roadmap/)

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