January 26, 2018—Today, the U.S. Food and Drug Administration (FDA) approved the use of lutetium-177–labeled dotatate (¹⁷⁷Lu-Dotatate) for the treatment of adult patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) including those of the foregut, midgut, and hindgut. ¹⁷⁷Lu-Dotatate, a form of peptide receptor radionucleotide therapy (PRRT), is a targeted radiation therapy that utilizes a somatostatin analogue (SSA) bound to a radiation-emitting isotope. This approval marks the first time a radiopharmaceutical has been approved for the treatment of GEP-NETs.
 
“GEP-NETs are a rare group of cancers with limited treatment options after initial therapy fails to keep the cancer from growing,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research in a press release announcing the approval. “This approval provides another treatment choice for patients with these rare cancers. It also demonstrates how the FDA may consider data from therapies that are used in an expanded access program to support approval for a new treatment.”
 
PRRT is able to deliver highly targeted radiation directly to somatostatin receptor-expressing cancer cells. After binding the receptor, the drug enters the cell, allowing direct radiation to the tumor cells. PRRT has been used widely in the European Union and Australia for years, and is now approved in the US.
 
This approval comes from results from the phase III NETTER-1 trial (ClinicalTrials.gov: NCT01578239; EudraCT: 2011-005049-11) in which 229 patients with well-differentiated metastatic midgut NETs were randomized to receive 7.4 GBq (gigabecquerel) of ¹⁷⁷Lu-Dotatate every 8 weeks in combination with octreotide or octreotide alone.
 
Results published in the New England Journal of Medicine last January showed progression-free survival at 20 months was 65.2% (95% CI, 50.0-76.8) for patients receiving PRRT compared with only 10.8% (95% CI, 3.5-23.0) for patients receiving traditional SSA therapy. Overall response rates were 18% and 3%, respectively. Patients treated with PRRT reported high-grade adverse events including lymphopenia (9%), thrombocytopenia (2%), and neutropenia (1%).
 
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Jonathan A. Bell
Published Online: Friday, January 26, 2018