On January 26th, the FDA approved a novel radioactive treatment, lutetium-177 dotatate (Lutathera), for patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) . GEP-NETs are rare tumors that develop from neuroendocrine cells that typically secrete large amounts of hormones and express high levels of somatostatin receptors, typically type II . Lutathera, developed and marketed by Advanced Accelerator Applications, is a somatostatin analog, dotatate, bound to a radioisotope, lutetium-177, that can bind to the somatostatin receptor with high affinity, delivering β-emitting radiation directly to GEP-NET cells within the body . Radiolabeled somatostatin analogs were first utilized to image GEP-NETs in vivo, and were then used in repeated, high doses to treat somatostatin receptor-positive tumors . Lutetium-177 dotatate was identified as an alternative to early radiolabeled somatostatin analogs that did not require repeated large doses for efficacy against GEP-NETs .
The approval was based on the results of a pivotal, randomized, open-label, international phase 3 clinical trial (NETTER-1) that compared Lutetium-177 dotatate plus standard therapy, octreotide LAR (somatostatin analog that blocks hormonal secretion) versus octreotide LAR alone in patients with midgut neuroendocrine tumor (NCT01578239) . The combination demonstrated an enhanced 20-month progression free survival rate over octreotide LAR monotherapy with 62.5% vs. 10.8%, respectively, and an improved response rate of 18% vs. 3%, respectively . Additionally, the combination was found to be well tolerated with an acceptable safety profile. This approval brings new therapeutic alternatives to patients with limited options and may provide a significant survival advantage over standard treatments.
–Zachary Moore, on behalf of the Medical Content Team
- LUTATHERA. Drugs@FDA: FDA Approved Drug Products January 26, 2018 [cited 2018 April 9]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208700s000lbl.pdf.
- Krenning, E.P., et al., Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med, 1993. 20(8): p. 716-31.
- Severi, S., et al., Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life. Onco Targets Ther, 2017. 10: p. 551-557.
- Krenning, E.P., et al., Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol, 1999. 10 Suppl 2: p. S23-9.
- Kwekkeboom, D.J., et al., Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol, 2008. 26(13): p. 2124-30.
- A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours (NETTER-1). ClinicalTrials.gov [cited 2018 April 9]; Available from: https://clinicaltrials.gov/ct2/show/NCT01578239.
- Strosberg, J., et al., Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med, 2017. 376(2): p. 125-135.