General Information

Lutathera (lutetium Lu 177 dotatate) is a radiolabeled somatostatin analog. 

Lutathera is specifically indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Lutathera is supplied as an injection for intravenous administration. The recommended dose is 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses. Please see drug label for premedication and use with concomitant medications.

Mechanism of Action

Lutathera (lutetium Lu 177 dotatate) is a radiolabeled somatostatin analog. Lutetium Lu 177 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells.

Side Effects

Adverse effects associated with the use of Lutathera may include, but are not limited to, the following:

• lymphopenia
• increased GGT
• vomiting
• nausea
• increased AST
• increased ALT
• hyperglycemia
• hypokalemia

Clinical Trial Results

The FDA approval of Lutathera was based on results of a randomized pivotal Phase III study, NETTER-1 that compared treatment using Lutathera plus best standard of care (octreotide LAR 30mg every four weeks) to 60 mg of octreotide LAR alone (also dosed every four weeks) in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors. The NETTER-1 study met its primary endpoint, showing a 79% reduction in risk of disease progression or death in the Lutathera arm compared to the 60 mg octreotide LAR arm (p<0.0001). Median PFS was not reached in the Lutathera arm compared to 8.5 months for the 60 mg octreotide LAR arm. A pre-planned interim overall survival analysis determined that Lutathera treatment lead to a 48% reduction in the estimated risk of death compared to treatment with 60 mg octreotide LAR. The objective response rate, composed of complete and partial responses, was 13% for the Lutathera arm compared to 4% in the Octreotide LAR 60mg arm (p<0.0148).