FDA Approves 177Lu-Dotatate in Patients 12 and Up for GEP-NETs

3D rendering of tumor microenvironment concept with cancer cells: © catalin - stock.adobe.com

• The FDA has approved lutetium Lu 177 dotatate (177Lu-Dotatate; Lutathera) for the treatment of pediatric patients 12 and older with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
• The approval is supported by findings from the NETTER-P (NCT04711135) study.
• This is the first FDA approval of a radiopharmaceutical for pediatric and adult patients with somatastatin receptor (SSTR)-positive GEP-NETs.

177Lu-Dotatate is the first radioactive drug approved for the treatment of patients 12 and older with SSTR-positive GEP-NETs.¹

The approval is supported by data from the NETTER-P study of the agent in adolescent patients with locally advanced and inoperable or metastatic SSTR-positive GETP-NETs or pheochromocytoma/paraganglioma.

Data from NETTER-1 (NCT01578239) of 177Lu-Dotatate in adult patients also support this approval. NETTER-1 supported the original approval of this agent in the adult population in 2018.

In NETTER-P, safety was evaluated in 9 pediatric patients, and 4 patients had GEP-NETs. Primary end points of the study were absorbed radiation doses in target organs and incidence of adverse events following the first treatment cycle. The safety profile of the agent was similar to what was reported in adults.

The application for 177Lu-Dotatate was granted priority review and orphan drug designation. The FDA has issued a postmarketing requirement to assess the long-term safety of 177Lu-Dotatate dotatate in the adolescent population.

The recommended dose is 7.4 GB1 (200 mCi) every 8 weeks for 4 doses.

3D rendering of tumor cell: ©nevio - stock.adobe.com

Findings from the primary analysis of NETTER-1 showed that 177Lu-Dotatate significantly improved progression-free survival vs high-dose long-acting octreotide in adult patients with advanced midgut GEP-NETs.²

Data from the phase 3 NETTER-2 trial (NCT03972488) were recently presented at the 2024 Gastrointestinal Cancers Symposium.³

Here, 177Lu-Dotatate delivered a median progression-free survival of 22.8 months (95% CI, 19.4-not evaluable [NE]) vs 8.5 months (95% CI, 7.7-13.8) with high-dose octreotide (stratified HR, 0.276; 95% CI, 0.182-0.418; P < .0001) among patients with grade 2 and 3 well-differentiated GEP-NETs, translating to a 72% reduction in the risk of disease progression or death with 177Lu-Dotatate vs high-dose octreotide.

In the 177Lu-Dotatate arm (n = 151), 47 progression events and 8 deaths occurred. In the high-dose octreotide arm (n = 75), 41 progression events and 5 deaths occurred.

REFERENCES:

1. FDA approves lutetium Lu 177 dotatate for pediatric patients 12 years and older with GEP-NETs. News release. FDA. April 23, 2024. Accessed April 23, 2024. https://tinyurl.com/y6mnj3zn

2. Strosberg J, Caplin M, Kunz P, et al. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. [published correction appears in Lancet Oncol. 2022 Feb;23(2):e59]. Lancet Oncol. 2021;22(12):1752-1763. doi:10.1016/S1470-2045(21)00572-6

3. Singh S, Halperin D, Myrehaug S, et al. [177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: primary analysis of the phase 3 randomized NETTER-2 study. J Clin Oncol. 2024(suppl 3):LBA588. doi:10.1200/JCO.2024.42.3_suppl.LBA588