On April 23, the U.S. Food and Drug Administration (FDA) approved lutetium Lu-177 dotatate (Lutathera) for pediatric patients aged 12 years and older with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors. Lu-177 dotatate received approval for this indication for adults in 2018.
This represents the first FDA approval of a radiopharmaceutical for pediatric patients aged 12 years of age and older with SSTR-positive GEP-NETs.
NETTER-P and NETTER-1
Approval was based on pharmacokinetic, dosimetry, and safety data from NETTER-P (ClinicalTrials.gov identifier NCT04711135), an ongoing, international, multicenter, open-label, single-arm study of Lu-177 dotatate in adolescent patients with locally advanced/inoperable or metastatic SSTR-positive GEP-NETs or pheochromocytoma/paraganglioma. Approval was also based on the extrapolation of efficacy outcomes observed in NETTER-1 (NCT01578239), a randomized, multicenter, open-label, active-controlled trial in 229 patients with locally advanced/inoperable or metastatic SSTR-positive midgut carcinoid tumors. Results from NETTER-1 also supported the original approval of Lu-177 dotatate in adult patients.
Safety was evaluated in nine pediatric patients enrolled in NETTER-P, including four patients with GEP-NETs. The major outcome measures were absorbed radiation doses in target organs and incidence of adverse reactions after the first treatment cycle. Additional outcome measures included short-term adverse reactions following treatment with Lu-177 dotatate. The adverse reaction profile observed in NETTER-P was similar to that observed in adults who received Lu-177 dotatate.
The recommended Lu-177 dotatate dose is 7.4 GBq (200 mCi) every 8 weeks (± 1 week) for a total of four doses. Premedications and concomitant medications should be administered as recommended. A postmarketing requirement was issued to assess the long-term safety of Lu-177 dotatate in adolescents.
NETTER-P was conducted as part of a pediatric written request under the Best Pharmaceuticals for Children Act. This application was granted Priority Review and Orphan Drug designation.
