On April 23, 2024, lutetium Lu-177 dotatate (Lutathera) was approved for pediatric patients 12 years and older with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors, including foregut, midgut, and hindgut neuroendocrine tumors.1 Lu-177 dotatate is a radiolabeled somatostatin analog. The agent was approved for adult patients in this setting in 2018.
Supporting Efficacy Data
Efficacy was extrapolated from the NETTER-1 trial (ClinicalTrials.gov identifier NCT01578239) in adult patients. The randomized, multicenter, open-label trial in 229 patients with locally advanced/inoperable or metastatic somatostatin receptor–positive midgut carcinoid tumors supported the 2018 approval in adult patients on the basis of improved progression-free survival with Lu-177 dotatate plus long-acting octreotide vs long-acting octreotide alone. Approval in pediatric patients was also based on pharmacokinetic, dosimetry, and safety data from adolescent patients with locally advanced/inoperable or metastatic somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors or pheochromocytoma/paraganglioma from the NETTER-P trial (NCT04711135).
How It Is Used
The recommended Lu-177 dotatate dose is 7.4 GBq (200 mCi) every 8 weeks (± 1 week) for a total of four doses. Product labeling provides instructions on premedication and concomitant medications, including use of long-acting and short-acting octreotide. Product labeling provides instructions on dosage modification for adverse reactions including thrombocytopenia, anemia, neutropenia, renal toxicity, hepatotoxicity, and hypersensitivity reactions.
Safety Profile
Among 111 adult patients receiving Lu-177 dotatate with octreotide in NETTER-1, the most common adverse events of any grade included nausea (65%), vomiting (53%), fatigue (38%), abdominal pain (26%), diarrhea (26%), and decreased appetite (21%). The most common grade 3 or 4 adverse events (≥ 4%) included lymphopenia, increased gamma-glutamyltransferase, vomiting, nausea, increased aspartate transaminase, increased alanine transaminase, hyperglycemia, and hypokalemia. Adverse events data from nine pediatric patients in NETTER-P were similar to those observed in adult patients. A postmarketing requirement was issued to assess the long-term safety of Lu-177 dotatate in adolescents.
OF NOTE
Lu-177 dotatate has warnings/precautions for risk from radiation exposure, myelosuppression, secondary myelodysplastic syndrome and leukemia, renal toxicity, hepatotoxicity, hypersensitivity reactions, neuroendocrine hormonal crisis, embryofetal toxicity, and risk of infertility.
Lu-177 dotatate has warnings/precautions for risk from radiation exposure, myelosuppression, secondary myelodysplastic syndrome and leukemia, renal toxicity, hepatotoxicity, hypersensitivity reactions, neuroendocrine hormonal crisis, embryofetal toxicity, and risk of infertility. Patients should be advised not to breastfeed while receiving Lu-177 dotatate.
REFERENCE
1. Lutathera (lutetium Lu 177 dotatate) injection, for intravenous use, prescribing information, Advanced Accelerator Applications USA, Inc, a Novartis company, April 2024. Available at https://us.lutathera.com/treatment/resources. Accessed May 14, 2024.
