Somatostatin analog peptide attached to a radioactive isotope. Used to treat gastroenteropancreatic neuroendocrine tumors that express somatostatin receptors.
Regulatory status
Approved (FDA / EMA)
Family
Radiopharmaceutical: somatostatin analog labeled with lutetium-177 (radioligand therapy)
FDA (US): Approved (2018, Lutathera) for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors in adults; later expanded to pediatric patients aged 12 years or older
EMA (EU): Approved (2017, Lutathera) for unresectable or metastatic, progressive, well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors
Dose
7.4 GBq (200 mCi) by intravenous infusion every 8 weeks, 4 doses in total, together with a somatostatin analog and an amino acid solution to protect the kidney (FDA/EMA label; NETTER-1 trial). Only in nuclear medicine departments.
Safety
Nausea and vomiting (partly from the amino acid infusion), drops in lymphocytes, platelets, and red blood cells, fatigue, and kidney toxicity. Rare but serious: myelodysplastic syndromes and leukemia years later. Requires radiation protection. Treatment exclusively in hospital and under the supervision of oncology and nuclear medicine.
Interactions
Long-acting somatostatin analogs compete for the same receptor: the label says to stop them several weeks before each dose. Corticosteroids may reduce receptor expression.
Differences between women and men
Contraindicated in pregnancy because of the radiation. The label calls for effective contraception in women during treatment and for about 7 months after the last dose, and in men with a fertile partner for about 4 months. It may affect fertility in both sexes. Breastfeeding is not recommended during treatment.
Effect by goal · level of evidence
Advanced midgut neuroendocrine tumors
improvesHighRCT (AA)in people
65% vs 11% progression-free at 20 months
NETTER-1 trial with 229 patients with metastatic midgut tumors. At 20 months, 65.2% with lutetium-dotatate were still progression-free vs 10.8% with high-dose octreotide. Objective response: 18% vs 3%.
First-line treatment in grade 2–3 gastroenteropancreatic tumors
improvesHighRCT (AA)in people
22.8 vs 8.5 months progression-free
NETTER-2 trial with 226 newly diagnosed patients. Median progression-free survival was 22.8 months with lutetium-dotatate plus octreotide vs 8.5 months with high-dose octreotide (HR 0.28).
The peptide portion binds to somatostatin receptors (mainly SSTR2), which are very abundant on these tumor cells. The drug enters the cell and lutetium-177 emits short-range beta radiation that damages tumor DNA. In this way the radiation is concentrated in the tumor and limited in healthy tissue.
What the evidence says
In people
Advanced midgut neuroendocrine tumors. NETTER-1 trial with 229 patients with metastatic midgut tumors. At 20 months, 65.2% remained progression-free with lutetium-dotatate versus 10.8% with high-dose octreotide. Objective response: 18% versus 3%. PubMed 28076709
First-line treatment in grade 2–3 gastroenteropancreatic tumors. NETTER-2 trial with 226 newly diagnosed patients. Median progression-free survival was 22.8 months with lutetium-dotatate plus octreotide versus 8.5 months with high-dose octreotide (HR 0.28). PubMed 38851203