From the Guidelines
Lutetium-177 (LU177) can be an effective treatment option for patients with neuroendocrine tumors (NETs) after Somatuline (lanreotide) stops working, as evidenced by the NETTER-1 trial which showed a significant improvement in progression-free survival (PFS) with LU177-DOTATATE compared to high-dose octreotide 1.
Key Points to Consider
- LU177 peptide receptor radionuclide therapy (PRRT) works through a different mechanism than somatostatin analogs like lanreotide, delivering targeted radiation directly to tumor cells expressing somatostatin receptors 1.
- Treatment typically involves four infusions of LU177-DOTATATE given eight weeks apart, with each session lasting 4-6 hours.
- Patients must still have sufficient somatostatin receptor expression on their tumors (confirmed by Gallium-68 DOTATATE PET scan) to benefit from this therapy.
- Common side effects include nausea, vomiting, and potential impacts on kidney function and blood counts, requiring monitoring throughout treatment.
- The NETTER-1 trial demonstrated a median PFS of 28.4 months with LU177-DOTATATE, compared to 8.5 months with high-dose octreotide, and also showed an improvement in symptoms and time to quality of life deterioration 1.
Clinical Considerations
- LU177 therapy is generally considered when patients show disease progression despite treatment with somatostatin analogs like lanreotide, making it a valuable second-line option.
- The decision to use LU177 should be based on individual patient factors, including tumor characteristics, prior treatment history, and overall health status.
- Close monitoring of patients during and after treatment is essential to manage potential side effects and assess treatment response. In summary, LU177 can be a effective treatment option for patients with NETs after lanreotide stops working, with a significant improvement in PFS and symptom control, as supported by the highest quality evidence from the NETTER-1 trial 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Effectiveness of Lutetium-177 (LU177) after Somatuline (Lanreotide) Stops Working
- The effectiveness of LU177 after Somatuline stops working can be evaluated based on several studies 2, 3, 4, 5, 6.
- A phase 3 trial published in 2017 found that LU177-Dotatate significantly improved progression-free survival and response rate compared to high-dose octreotide LAR in patients with advanced midgut neuroendocrine tumors who had disease progression during first-line somatostatin analogue therapy 2.
- A literature review published in 2019 noted that LU177-Dotatate has shown better results in advanced gastroenteropancreatic and bronchial neuroendocrine tumors compared to other therapies available, with adverse effects including myelotoxicity and nephrotoxicity 3.
- A practice parameter published in 2022 provided guidance on the use of LU177-Dotatate for adult candidates with gastroenteropancreatic neuroendocrine tumors, including those who have progressed despite standard therapy 4.
- A final overall survival and long-term safety analysis of the NETTER-1 trial published in 2021 found that LU177-Dotatate plus long-acting octreotide did not significantly improve median overall survival compared to high-dose long-acting octreotide alone, but may be considered clinically relevant 5.
- A study published in 2022 found that LU177-DOTATATE achieved a meaningful disease control rate of 72% in patients with well-differentiated high-grade neuroendocrine tumors, with toxicities largely bone marrow-related 6.
Key Findings
- LU177-Dotatate can be effective in patients with advanced neuroendocrine tumors who have progressed despite standard therapy, including those who have stopped responding to Somatuline 2, 3, 4.
- The treatment has shown significant improvements in progression-free survival and response rate compared to other therapies 2, 3.
- Adverse effects of LU177-Dotatate include myelotoxicity and nephrotoxicity, but are generally manageable 3, 5, 6.
- The treatment may be considered clinically relevant even if it does not significantly improve overall survival, due to its ability to control disease progression and improve symptoms 5.