Abstract. NEOLUPANET was a multicentre, single-arm, phase II trial, conducted between March 2020 and February 2023 at eight Italian institutions. Patients- non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) at high risk of recurrence, with positive uptake on 68Ga-labelled DOTA PET. They underwent neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) therapy followed by surgical resection at an acceptable complication rate, with no postoperative death. The majority of patients had a partial response without any progressive disease.
Neoadjuvant means treatment given as a first step to shrink a tumour before the main treatment, which is usually surgery.
NF-PanNETs are more common than their functional counterparts. NF-PanNETs display variable biological behaviour, ranging from indolent, small, and asymptomatic tumours, which can be managed through active surveillance, to aggressive lesions requiring radical surgical treatment. The recurrence rate after surgery is around 20–30%. No established adjuvant therapy protocols are available to reduce this risk. Thus why the trial is interesting, albeit only on a small cohort of patients.
It’s also interesting because most guidelines urge caution in surgical intervention in many NF-PanNETs less than 2cm. However, the clinical trial document confirms the target population:
And it would be remiss of me to exclude the output of the NETTER-2 clinical trial where it was suggesting a neoadjuvant approach to Grade 2 and 3 NETs using SSTR radioligand therapy (PRRT) as a first line treatment. The output from that trial said “There are currently no standard first-line treatment options for patients with higher grade 2–3, well-differentiated, advanced, gastroenteropancreatic neuroendocrine tumours. We aimed to investigate the efficacy and safety of first-line [177Lu]Lu-DOTA-TATE (177Lu-Dotatate) treatment.” and then concluded “First-line 177Lu-Dotatate plus octreotide LAR significantly extended median progression-free survival (by 14 months) in patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumours. 177Lu-Dotatate should be considered a new standard of care in first-line therapy in this population.”
Read the cited NEOLUPANET study below (click on the blue highlighted text).
Stefano Partelli, Luca Landoni, Mirco Bartolomei, Alessandro Zerbi, Chiara Maria Grana, Ugo Boggi, Giovanni Butturini, Riccardo Casadei, Roberto Salvia, Massimo Falconi, Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study, British Journal of Surgery, Volume 111, Issue 9, September 2024, znae178, https://doi.org/10.1093/bjs/znae178
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