The NETTER-2 study

Prof Timon van Damme, a digestive oncologist at the University Hospital in Antwerp, discusses the groundbreaking NETTER-2 trial presented by Prof. Wouter de Herder from Erasmus MC Hospital, Rotterdam at ENETS 2024. This trial investigates the efficacy of peptide-receptor radiotherapy (PRRT) in grade 2 and grade 3 well-differentiated neuroendocrine tumours (NETs) compared to high-dose somatostatin analogues, serving as a first-line treatment.

The trial randomised patients to receive either PRRT (177Lutetium DOTATATE) or high-dose somatostatin analogues, with a notable two-to-one randomisation ratio favouring PRRT. The primary endpoint was progression-free survival, with the trial allowing for crossover and additional PRRT cycles upon progression, novel strategies not present in previous trials like NETTER1.

Results revealed a significant benefit in progression-free survival, with the PRRT arm showing 22 months compared to 9 months in the somatostatin analogue group. This trial is pivotal as it marks the first use of PRRT in a first-line setting, particularly in high-grade, well-differentiated NETs, where previous treatment data were lacking.

Prof Van Damme underscores the significance of having two viable treatment options: high-dose somatostatin analogues and PRRT, with the latter especially promising for patients with high tumour burden. However, he acknowledges the potential side effects of PRRT, including initial nausea and a limited risk of myelodysplastic syndrome, compared to the well-tolerated nature of somatostatin analogues.

The findings prompt further investigation into optimal treatment strategies for high-grade NETs, yet the availability of the first randomised data in this population marks a significant advancement in guiding clinical decision-making.