Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET
Summary
The aim of NETTER-2 was to determine if Lutathera in combination with long-acting octreotide prolongs progression free survival (PFS) in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients were eligible, as well as patients previously treated with SSAs in the absence of progression.
Timeline
- Start
- 2020-01-08
- Primary completion
- 2023-07-20
- Completion
- 2027-10-29
Outcome
Met primary endpoint
paper Median progression-free survival was 8·5 months (95% CI 7·7-13·8) in the control group and 22·8 months (19·4-not estimated) in the 177Lu-Dotatate group (stratified hazard ratio 0·276 [0·182-0·418]; p<0·0001). PMID 38851203 ↗
release “Phase III NETTER-2 trial met primary endpoint of improvement in progression-free survival (PFS) and key secondary endpoint of objective response rate” novartis.com ↗
Publications
- Results Singh S, Halperin D, Myrehaug S, Herrmann K, Pavel M, Kunz PL, Chasen B, Tafuto S, Lastoria S, Capdevila J, Garcia-Burillo A, Oh DY, Yoo C, Halfdanarson TR, Falk S, Folitar I, Zhang Y, Aimone P, de Herder WW, Ferone D; all the 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 Jun 29;403(10446):2807-2817. doi: 10.1016/S0140-6736(24)00701-3. Epub 2024 Jun 5.
- Holzgreve A, Unterrainer LM, Tiling M, Mansour N, Spitzweg C, Brendel M, Ricke J, Unterrainer M, Kunz WG, Mehrens D. Cost-Effectiveness of [177Lu]Lu-DOTATATE for the Treatment of Newly Diagnosed Advanced Gastroenteropancreatic Neuroendocrine Tumors: An Analysis Based on Results of the NETTER-2 Trial. J Nucl Med. 2025 Jul 1;66(7):1075-1081. doi: 10.2967/jnumed.124.269416.
- Bahri N, Crook C, Daneng Li. Casting a Wide NET: When Is the Optimal Time for 177Lu-Dotatate Treatment? Oncology (Williston Park). 2024 Nov 5;38(11):442-443. doi: 10.46883/2024.25921029.
- Jungels C, Deleporte A. State of the art and future directions in the systemic treatment of neuroendocrine neoplasms. Curr Opin Oncol. 2021 Jul 1;33(4):378-385. doi: 10.1097/CCO.0000000000000740.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | 177Lu-DOTATATE | Peptide | 7400 mbq | Intravenous |
| Comparator | Octreotide | Peptide | 30 mg | Intramuscular |
| Comparator | Octreotide | Peptide | 60 mg | Intramuscular |
| Background | Lys-Arg | Unknown | 2.5 % | Intravenous |