FDA Approves Lutathera for Gastroenteropancreatic Neuroendocrine Tumors

February 1, 2018

The US Food and Drug Administration approved lutetium Lu 177 dotatate (Lutathera) for the treatment of somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors in adults.

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).

VIDEO: Jonathan Strosberg, MD, Discussing Results of NETTER-1

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.