The European Commission (EC) has approved the marketing authorisation of lutetium (¹⁷⁷Lu) oxodotreotide (Lutathera) for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults.

This approval allows for the marketing of lutetium oxodotreotide in all 28 European Union member states, as well as Iceland, Norway and Liechtenstein.

The approval is based on results of a randomised pivotal phase 3 study, NETTER-1 that compared treatment using lutetium oxodotreotide with a double dose of Octreotide LAR in patients with inoperable midgut NETs progressive under standard Octreotide LAR treatment and overexpressing somatostatin receptors, as well as efficacy and safety data from the Erasmus Phase 1/2 trial conducted in more than 1,200 patients with a wide range of NET indications including foregut (including bronchial and pancreatic), midgut and hindgut.

The European Medicines Agency requested an update of NETTER-1 efficacy results with a cut-off date of June 30, 2016.

The findings of this update were consistent with previously published results.

The NETTER-1 study met its primary endpoint, showing a reduction of risk of progression or death of 79% using lutetium oxodotreotide compared to octreotide LAR 60 mg.

Although the final Overall Survival (OS) analysis (secondary endpoint) is planned for after the first of either 158 cumulative deaths, or five years after the last patient is randomized; the current update (after 71 cumulative deaths), also confirmed the favourable trend of 28 deaths in the lutetium oxodotreotide arm versus 43 in the octreotide LAR 60 mg arm.

The median OS in the octreotide LAR arm was 27.4 months, but was still not reached in the lutetium arm after 42 months, with a Hazard Ratio (HR) of 0.536, meaning a reduction of risk of death of 46% using lutetium compared to octreotide LAR 60 mg.

Martyn Caplin, Professor of gastroenterology and GI neuroendocrinology at the Royal Free London and University College London and Vice Chair (former Chairman) of the European Neuroendocrine Tumour Society, stated, “There are very few effective treatment options for patients with inoperable, advanced GEP-NETs who are progressive on somatostatin analogues. Having this therapy approved and available will offer physicians a further option to help manage their patients’ disease.”

Gastroenteropancreatic neuroendocrine tumours, also known as GEP-NETs, are a group of tumours originating in the neuroendocrine cells of numerous organs.

Lutathera has received orphan drug designation from the European Medicines Agency.

The estimated incidence of gastrointestinal NETs in the UK is approximately 2.65 per 100,000 per year, while the estimated incidence of pancreatic NETs in the UK is less than 0.2 per 100,000 per year.

However, since NETs are often slow-growing and associated with prolonged survival, the prevalence of NETs is relatively high.

Catherine Bouvier, Chief Executive Officer of NET Patient Foundation, a NET patient advocacy group/charity in the UK, noted, “The NET patient community welcomes the approval of Lutathera. Due to the orphan nature of NETs and difficulty in obtaining proper diagnosis, many patients are not diagnosed until their disease has become quite advanced. Disease progression significantly impacts quality of life and limits the time with family and friends.”

Source: Advanced Accelerator Applications