Drugs Xagena
The Food and Drug Administration ( FDA ) has approved Lutathera ( Lutetium Lu 177 Dotatate ), a radiolabeled Somatostatin analog, for the treatment of Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors ( GEP-NETs ), including foregut, midgut, and hindgut neuroendocrine tumors in adults.
Approval was based on data from NETTER-1, a randomized, multicenter, open-label, active-controlled trial in 229 patients with progressive, well-differentiated, locally advanced / inoperable or metastatic Somatostatin receptor-positive midgut carcinoid tumors.
Patients were randomized ( 1:1 ) to receive either Lutetium Lu 177 Dotatate ( 7.4 GBq [ 200 mCi ] every 8 weeks for up to 4 administrations; maximum cumulative dose of 29.6 GBq ) with long-acting Octreotide ( 30 mg by intramuscular injection every 4 weeks ) or high-dose long-acting Octreotide ( 60 mg by intramuscular injection every 4 weeks ).
Lutetium Lu 177 Dotatate was co-administered with an amino acid solution as a renal protectant. In the US, patients enrolled in NETTER-1 received Aminosyn II 10%, a solution of amino acids.
The major efficacy outcome measure was progression free survival ( PFS ) determined by a blinded independent radiology Committee using RECIST 1.1.
The median progression free survival was not reached for Lutetium Lu 177 Dotatate and was 8.5 months in the high-dose long-acting Octreotide arm ( hazard ratio, HR=0.21; 95% CI: 0.13, 0.32; p less than 0.0001 ).
The efficacy of Lutetium Lu 177 Dotatate was also assessed in a subset ( n=360 ) of 1214 patients enrolled in the ERASMUS Medical Center ( MC ) study with GEP-NET tumors who were assessed according to RECIST criteria.
At the ERASMUS MC, Lutetium Lu 177 Dotatate was initially provided as expanded access under a general peptide receptor radionuclide therapy protocol at a single site in the Netherlands.
Lutetium Lu 177 Dotatate ( 7.4 GBq [ 200 mCi ] ) was administered every 6 to 13 weeks for up to 4 doses.
The ORR was 16% ( n=58 ), including 3 complete responses in this subset of 360 patients with GEP-NETs who were assessed according to RECIST criteria.
In the NETTER-1 study, the most common grade 3-4 adverse reactions occurring with a greater frequency ( at least 4% ) among patients receiving Lutetium Lu 177 Dotatate with long-acting Octreotide compared to patients receiving high-dose Octreotide alone included lymphopenia ( 44% ), increased GGT ( 20% ), vomiting ( 7% ), nausea and elevated AST ( 5% each ), and increased ALT, hyperglycemia, and hypokalemia ( 4% each ).
In NETTER-1, with a median follow-up of 24 months, myelodysplastic syndrome was reported in 2.7% of patients receiving Lutetium Lu 177 Dotatate with long-acting Octreotide; no patients receiving high-dose Octreotide LAR developed myelodysplastic syndrome.
The recommended dose of Lutetium Lu 177 Dotatate is 7.4 GBq ( 200 mCi ) as an intravenous infusion over 30 minutes every 8 weeks for a total of 4 doses.
FDA granted priority review for this application and previously granted Orphan Drug designation to Lutetium Lu 177 Dotatate for treatment of GEP-NETs. ( Xagena )
Source: FDA, 2018
XagenaMedicine_2018
