177Lu Dotatate is a radiolabeled somatostatin analog peptide approved by the FDA for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults. 177Lu Dotatate binds to somatostatin receptors that are often overexpressed on neuroendocrine tumor cells. After binding to the receptors, 177Lu emits targeted radiation directly to the tumor cells while limiting radiation exposure to normal healthy tissues.
The FDA initially approved 177Lu Dotatate in 2018 based on the results of the NETTER-1 phase 3 trial. This was a randomized, multicenter, open-label study comparing treatment with 177Lu Dotatate plus long-acting octreotide versus high-dose long-acting octreotide alone in patients with inoperable, progressive, somatostatin receptor-positive midgut NETs.
The trial showed that 177Lu Dotatate significantly improved progression-free survival compared to octreotide alone. The estimated rate of progression-free survival at month 20 was 65.2% in the 177Lu Dotatate arm vs 10.8% in the control arm. Objective response rates were also higher with 177Lu Dotatate (18%) than octreotide alone (3%). This led to the 2018 FDA approval of 177Lu Dotatate for the treatment of somatostatin receptor-positive GEP-NETs, including foregut, midgut, and hindgut neuroendocrine tumors.
In 2022, the FDA expanded the approval of 177Lu Dotatate to include the treatment of somatostatin receptor-positive lung and gastrointestinal NETs. This was based on the phase 3 LIGHT trial, which demonstrated clinically meaningful benefit with 177Lu Dotatate in these additional patient populations.
The LIGHT trial compared treatment with 177Lu Dotatate to high-dose long-acting octreotide in patients with progressive, metastatic lung or gastrointestinal NETs. The study met its primary endpoint, showing improved progression-free survival with 177Lu Dotatate compared to octreotide. Rates of objective response were also significantly higher with 177Lu Dotatate.
Based on these results, the FDA approved 177Lu Dotatate for treating adult patients with somatostatin receptor-positive gastrointestinal or lung NETs, expanding the indications beyond midgut NETs.
177Lu Dotatate is administered intravenously, typically in 4 doses every 8 weeks. It is generally well tolerated, with most adverse effects related to damage of normal somatostatin receptor-positive cells. Common side effects include nausea, vomiting, headache, fatigue, and cytopenias such as lymphopenia, anemia, or thrombocytopenia. Proper patient selection and monitoring can help mitigate risks.
Overall, 177Lu Dotatate provides an important therapeutic option for patients with somatostatin receptor-positive NETs originating from the GI tract, lungs or pancreas. Its ability to deliver targeted radiation directly to tumors makes it an effective treatment approach for these hard-to-treat cancers. The NETTER-1 and LIGHT trials clearly demonstrated the benefits of 177Lu Dotatate in improving progression-free survival and response rates compared to prior standard therapies.
If you or a loved one has been diagnosed with a neuroendocrine tumor, be sure to ask your care team if 177Lu Dotatate may be an appropriate part of your personalized treatment plan. Advances like this radionuclide therapy are providing new hope for patients with metastatic NETs.
At The Hormone Hub, we specialize in providing comprehensive care for patients with all types of neuroendocrine tumors, including carcinoids, pheochromocytomas, and pancreatic NETs. Our experienced physicians use advanced technologies like 177Lu Dotatate peptide receptor radionuclide therapy to target your specific tumor type and provide the most effective treatments. Contact us today to learn more about our NET therapy program and the latest options that may help control your disease.
