1186MO - A prospective phase II single-arm trial on neoadjuvant peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE followed by surgery for pancreatic neuroendocrine tumors (NeoLuPaNET)

Background

Surgical resection of Nonfunctioning Pancreatic Neuroendocrine Tumor (NF-PanNET) is curative in most of the cases. Neoadjuvant treatments in patients with resectable NF-PanNET at high-risk of recurrence have never been investigated. Aim of this study was to test the safety and efficacy of neoadjuvant PRRT with ¹⁷⁷Lu-DOTATATE followed by surgery in patients with resectable high-risk NF-PanNET.

Methods

This was a multi-center single-arm phase 2 trial. Treatment was PRRT with ¹⁷⁷Lu-DOTATATE (Lutathera) followed by surgery in patients with high-risk of recurrence resectable NF-PanNET. “High-risk NF-PanNET” was defined by the presence of at least one of the following: tumor size > 4 cm, nearby organ/s invasion, Ki67 >10%, vascular invasion, single liver metastasis, nodal involvement. Primary endpoints were postoperative morbidity and mortality. Secondary endpoint was the rate of objective radiological response.

Results

Thirty-one patients were enrolled in the study. Twenty-six (84%) tolerated 4 cycles of ¹⁷⁷Lu-DOTATATE whereas 4 patients did not complete 4 cycles for adverse events. One patient voluntary interrupted treatment after 2 cycles. A partial radiological response was observed in 17 patients (59%) whereas no disease progression occurred. Two patients refused to undergo surgery after ¹⁷⁷Lu-DOTATATE. Eventually, 29 patients underwent surgery after a median period of 281 days (261.5–309 days) from the enrollment. Resection of NF-PanNET was achieved in 28 patients (96.5%) whereas one patient underwent exploratory laparotomy. Pancreaticoduodenectomy (n= 11) and distal pancreatectomy (n= 11) were the most frequent operations. At final histology, the majority of patients had a NF-PanNET G2 (n= 16) and a nodal involvement (N1) was present in the 52% of cases. There was no postoperative mortality. Severe postoperative complications occurred in the 24% of patients and postoperative pancreatic fistula was the most frequent complication after surgery (34%).

Conclusions

Neoadjuvant PRRT with ¹⁷⁷Lu-DOTATATE followed by surgery for NF-PanNET is safe and effective demonstrating evidence of a high rate-of radiological response.

Clinical trial identification

NCT04385992.

Editorial acknowledgement

Legal entity responsible for the study

Massimo Falconi.

Funding

Advanced Accelerator Applications (a Novartis company).

Disclosure

All authors have declared no conflicts of interest.