Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study

Background: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant Lu-177-labelled DOTA(0)-octreotate (Lu-177-DOTATATE) followed by surgery in patients with NF-PanNETs. Methods: NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive Ga-68-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant Lu-177-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. Results: From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of Lu-177-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after Lu-177-DOTATATE and decreased after surgery. Conclusion: Neoadjuvant treatment with Lu-177-DOTATATE is safe and effective for patients with NF-PanNETs.