In patients with advanced, progressive, somatostatin receptor-positive midgut neuroendocrine tumors, treatment with lutetium-177 (177Lu)–Dotatate significantly improved progression-free survival and overall response rate compared with high-dose octreotide long-acting repeatable (LAR), a study published in The New England Journal of Medicine has shown.1

Patients with advanced midgut neuroendocrine tumors who have experienced disease progression during first-line treatment with a somatostatin analogue have limited therapeutic options. 177Lu–Dotatate is a peptide receptor radionuclide therapy that demonstrated encouraging efficacy in a phase 2 trial. Therefore, researchers sought to evaluate the efficacy and safety of 177Lu–Dotatate in a phase 3 trial.

For the open-label NETTER-1 clinical trial (ClinicalTrials.gov Identifier: NCT01578239), investigators enrolled 229 patients with well-differentiated, metastatic midgut neuroendocrine tumors. Participants were randomly assigned 1:1 to 177Lu-Dotatate at a dose of 7.4 GBq every 8 weeks for 4 doses plus best supportive care, including intramuscular octreotide LAR given at a dose of 30 mg, or octreotide LAR alone at a dose of 60 mg every 4 weeks.

Researchers estimated that 65.2% (95% CI, 50.0-76.8) of patients in the 177Lu-Dotatate group would be progression-free at month 20 compared with 10.8% (95% CI, 3.5-23.0) in the octreotide LAR alone group.

Results further showed that a significantly higher proportion of patients who received radionuclide therapy achieved a response than those in the control arm (18% vs 3%; P <.001).

A planned interim analysis also demonstrated that treatment with 177Lu-Dotatate may be associated with an overall survival benefit; however, the planned final analysis is required for confirmation.

Fewer than 10% of patients in the 177Lu-Dotatate group experienced clinically significant myelosuppression. Grade 3 to 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the experimental arm vs no patients in the control arm. Investigators observed no evidence of renal toxicity during the study period.

Reference

1. Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376:125-135.