On 23 April 2024, the US Food and Drug Administration (FDA) approved lutetium Lu 177 dotatate (Lutathera, Advanced Accelerator Applications USA, Inc., a Novartis company) for paediatric patients 12 years and older with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumours. Lutetium Lu 177 dotatate received approval for this indication for adults in 2018.
This represents the first FDA approval of a radioactive drug, or radiopharmaceutical, for paediatric patients 12 years of age and older with SSTR-positive GEP-NETs.
Approval was based on pharmacokinetic, dosimetry, and safety data from NETTER-P (NCT04711135), an ongoing, international, multicentre, open-label, single-arm study of lutetium 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 randomised, multicentre, open-label, active-controlled study in 229 patients with locally advanced/inoperable or metastatic SSTR-positive midgut carcinoid tumours, which supported the original approval of lutetium Lu 177 dotatate in adult patients.
Safety was evaluated in 9 paediatric patients in NETTER-P, including 4 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 lutetium Lu 177 dotatate. The adverse reaction profile observed in NETTER-P was similar to that observed in adults.
The recommended lutetium Lu 177 dotatate dose is 7.4 GBq (200 mCi) every 8 weeks (± 1 week) for a total of 4 doses. Premedications and concomitant medications should be administered as recommended. A post-marketing requirement was issued to assess the long-term safety of lutetium Lu 177 dotatate in adolescents.
NETTER-P was conducted as part of a paediatric Written Request under the Best Pharmaceuticals for Children Act. This application was granted priority review and orphan drug designation.
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