The FDA has approved lutetium Lu 177 dotatate (Lutathera, Advanced Accelerator Applications S.A.) for the treatment of somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.
Lutathera, which received an orphan drug designation from the FDA, is a first-in-class drug and the first FDA-approved peptide receptor radionuclide therapy (PRRT), a form of targeted treatment comprising a targeting molecule that carries a radioactive component.
NETs are rare tumors originating in the neuroendocrine cells of numerous organs, including the gastrointestinal tract, pancreas, and lung. Some patients develop symptoms arising from the excessive production of hormones by neuroendocrine tumor cells, while others remain clinically silent for years. The estimated incidence of new cases of NETs in the United States is approximately 6.98 per 100,000 people per year. Patients with well- and moderately-differentiated tumors and distant metastases have a five-year survival probability of 35%.
The company radiolabeled the same targeting molecule with either lutetium 177 or gallium 68, respectively, for therapeutic or diagnostic purposes.
The approval is based on results of a randomized, pivotal, phase 3 study, NETTER-1, that compared treatment using Lutathera plus best standard of care (octreotide LAR 30 mg every four weeks) to 60 mg of octreotide LAR alone (also dosed every four weeks) in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors.
The NETTER-1 study met its primary endpoint, showing a 79% reduction in risk of disease progression or death in the Lutathera arm compared to the 60-mg octreotide LAR arm (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.13–0.32; P < 0.0001). Median progression-free survival was not reached in the Lutathera arm compared to 8.5 months for the 60-mg octreotide LAR arm. A pre-planned interim overall survival analysis determined that Lutathera treatment lead to a 48% reduction in the estimated risk of death (HR, 0.52; 95% CI, 0.32–0.84) compared to treatment with 60-mg octreotide LAR. The objective response rate, composed of complete and partial responses, was 13% for the Lutathera arm compared to 4% in the Octreotide LAR 60 mg arm.
The most common grade 3-4 adverse reactions occurring with a greater frequency among patients in the NETTER-1 study receiving Lutathera with octreotide compared to patients receiving high-dose octreotide include: lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea and elevated aspartate aminotransferase (5% each), and increased alanine aminotransferase, hyperglycemia and hypokalemia (4% each).
The new drug application also included a subset of efficacy and safety data from an international, single-institution, single-arm, open-label trial conducted by Erasmus Medical Center in Rotterdam, Netherlands, in more than 1,200 patients with somatostatin receptor positive tumors.
Source: Advanced Accelerator Applications S.A., January 26, 2018