The US Food and Drug Administration (FDA) approved lutetium Lu 177 dotatate (Lutathera) for the treatment of somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults.
Lutetium Lu 177 dotatate is a radiolabeled somatostatin analog. It is the first FDA-approved peptide receptor radionuclide therapy (PRRT), a form of targeted treatment comprising a targeting molecule that carries a radioactive component. The approval included tumors of the foregut, midgut, and hindgut.
The FDA based its approval on data from the NETTER-1 trial, which included 229 patients with progressive, well-differentiated, locally advanced, inoperable, or metastatic somatostatin receptor–positive midgut carcinoid tumors. Patients were randomly assigned to lutetium Lu 177 dotatate every 8 weeks for up to 4 administrations plus long-acting octreotide, or the standard of care: high-dose long-acting octreotide. The primary efficacy endpoint was progression-free survival.
The median progression-free survival as assessed by a blinded independent radiology committee was not yet reached in patients assigned lutetium Lu 177 dotatate compared with 8.5 months in the high-dose long-acting octreotide group. This translated into a 79% reduction in the risk of disease progression or death (hazard ratio [HR], 0.21; 95% CI, 0.13–0.32; P < .0001).
The study also included a pre-planned interim analysis of overall survival that showed a 48% reduction in the risk of death with lutetium Lu 177 dotatate (HR, 0.52; 95% CI, 0.32–0.84) compared with standard of care. The objective response rate with lutetium Lu 177 dotatate was 13% compared with 4% for high-dose long-acting octreotide (P < .0148).
The most common grade 3/4 adverse events in the intervention arm of NETTER-1 were lymphopenia (44%), increased gamma-glutamyltransferase (20%), vomiting (7%), nausea (5%), and elevated AST (5%). In addition, with a median follow-up of 2 years, 2.7% of patients in the lutetium Lu 177 dotatate arm developed myelodysplastic syndromes compared with no patients in the comparison arm.
The efficacy of lutetium Lu 177 dotatate was also evaluated in a subset of 360 patients enrolled in a study of GEP-NET tumors at the Erasmus Medical Center in the Netherlands. In this study, lutetium Lu 177 dotatate was initially provided as expanded access under a general PRRT protocol. Patients received lutetium Lu 177 dotatate every 6 to 13 weeks for up to 4 doses. Patients had an overall response rate of 16%, including three complete responses.
“There are very few effective treatment options for patients with inoperable, advanced GEP-NETs who are progressive on somatostatin analogues,” said Jonathan Strosberg, MD, section head of the Neuroendocrine Tumor Program at Moffitt Cancer Center in Tampa, Florida, and NETTER-1 lead investigator, in a press release. “As a medical oncologist seeing more than 500 patients with NETs each year, I am grateful to have another tool in my arsenal.”
The FDA has recommended a dose of lutetium Lu 177 dotatate of 7.4 GBq as an intravenous infusion over 30 minutes every 8 weeks for four doses.