As a rare cancer, treatment options for neuroendocrine tumour (NET) after failing initial therapy had been limited. Not until 2018, the Food and Drug Administration (FDA) approved a peptide receptor radionuclide therapy (PRRT), lutetium-177 dotatate for adult patients with advanced NETs affecting the pancreas or gastrointestinal tract. PRRT is a type of targeted radionuclide therapy which involves the systemic administration of therapeutic peptides labelled with radionuclides that selectively target cancer cells. The receptor-peptide complex is internalized via endocytosis and the radionuclide is preferentially retained by the receptor-expressing tumour cells. This process can lead to cell death, as the radiation-particles released by radionuclide primarily cause DNA single-strand breaks. Majority of NETs express somatostatin receptor, therefore radiolabelled somatostatin analogs are the preferred choice for PRRT. Beta particles are released by lutetium-177 in these tumour cells.
Benefit for lutetium-177 dotatate was shown in the phase III international NETTER-1 trial. 230 patients with inoperable, somatostatin-receptor-positive gastrointestinal NETs who experienced progressive disease on standard doses of octreotide LAR (i.e., 30 mg every 28 days) were randomly assigned to lutetium-177 dotatate plus continuation of standard dose of octreotide LAR or octreotide LAR 60 mg every 28 days. The estimated PFS rate at month 20 was significantly higher with lutetium-177 dotatate (65.2 versus 10.8 %, hazard ratio 0.21 [95% confidence interval 0.13-0.33]). Lutetium-177 dotatate also associated with a significantly higher objective response rate (18 versus 3 %). The most common adverse event in the Lutetium-177 dotatate group was nausea (all grade: 59%; grade 3/4: 4 %), thought to be due to the amino acid infusions administered during therapy to protect the kidneys. Hematologic toxicities included mostly mild degrees of thrombocytopenia (25%), lymphopenia (all grade: 18%; grade 3/4: 9%, anemia (14%), and leukopenia (10%).
