NETTER-1: 177Lu-Dotatate for midgut neuroendocrine tumours progressing on octreotide
Radioligand therapy with lutetium-177 dotatate reduced the risk of progression or death by nearly 80 percent compared with high-dose octreotide in midgut neuroendocrine tumours, the first randomised proof that targeted radiation works in these cancers.
Overview
Phase 3 trial of 229 patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumours randomised to four cycles of 177Lu-Dotatate plus octreotide LAR 30 mg or high-dose octreotide LAR 60 mg.
Progression-free survival at 20 months was 65.2 versus 10.8 percent (hazard ratio 0.21), response 18 versus 3 percent, and an interim analysis suggested improved overall survival; myelosuppression was modest.
- Progression-free survival hazard ratio 0.21; 20-month rate 65.2 percent vs 10.8 percent.
- Objective response 18 percent vs 3 percent.
Lutetium-177 dotatate is a standard treatment for progressive small bowel neuroendocrine tumours after somatostatin analogues, and NETTER-2 has since moved it into first-line use for higher-grade tumours.
- Final overall survival difference (48.0 vs 36.3 months) did not reach significance, partly because of crossover.
- Rare late myelodysplasia and leukaemia.
People treated with the radioactive drug lutetium-177 dotatate kept feeling well for much longer - years rather than months, in several measures - than people on the standard high-dose hormone injection, on top of the tumour-control benefit already shown.
In the largest reported group of neuroendocrine tumour patients treated with individually dosed radioactive peptide therapy, most people lived several years after treatment, and serious long-term harms such as blood cancers were uncommon but real, occurring in about 1 in 50 patients.
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