The developing role of theranostics in NETs

Neuroendocrine tumours (NETs) are categorised as rare tumours, but the incidence continues to increase.1 Most commonly, these tumours arise within the gastrointestinal tract or pancreas and are collectively known as gastroenteropancreatic NETs.1 These tumours are classified by WHO into grades according to mitotic index, differentiation status and Ki67 proliferative index, which translates into aggressiveness.2 For patients with advanced disease, few treatment options exist but include somatostatin analogues, targeted therapy, chemotherapy, and peptide receptor radionuclide therapy (PRRT).3–8 Furthermore, the change in the WHO grade 3 classification into well and poorly differentiated tumours makes the current optimal treatment for well differentiated grade 3 gastroenteropancreatic NETs undefined.2 The phase 3 NETTER-1 trial, as reported by Strosberg and colleagues, randomly assigned patients with progressive grade 1–2 midgut NETs to PRRT using [177Lu]Lu-DOTA-TATE (177Lu-Dotatate) with octreotide long-acting repeatable (LAR) versus high dose octreotide LAR (60 mg).8 This study showed a substantial benefit in progression-free survival. The primary endpoint was progression-free survival, with the secondary endpoints of overall response rate, time to deterioration of quality of life, disease control rate, duration of response, safety, and overall survival; crossover was allowed following confirmed progression by central review. [...]of the primary analysis, the median overall survival had not yet been reached for either group, but no difference in overall survival was observed between the treatment groups at follow-up.