Efficacy and safety of <sup>177</sup>Lu-DOTATATE in patients (pts) with advanced pancreatic neuroendocrine tumors (pNETs): Data from the NETTER-R international, retrospective registry.
Authors: Dominique Clement, Shaunak Navalkissoor, Rajaventhan Srirajaskanthan, Frédéric Courbon, Lawrence Dierickx, Amy Eccles, Valerie Lewington, Mercedes Mitjavila, Juan Carlos Percovich, Benoît Lequoy, Beilei He, Ilya Folitar, John Ramage
Journal: Journal of Clinical Oncology (2021)

4116 Background: Peptide receptor radionuclide therapy with 177 Lu-DOTATATE is indicated in somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumours. The NETTER-R registry builds upon the existing evidence for pts with advanced pNETs, who have limited therapeutic options. Methods: NETTER-R is a retrospective registry of pts with unresectable or metastatic, well-differentiated, SSTR-positive, progressive pNETs treated with 177 Lu-DOTATATE in the UK, France and Spain. Pts who received ≥1 administration of 177 Lu-DOTATATE were included. The primary endpoint was progression-free survival (PFS) based on RECIST v1.1. Secondary endpoints included overall survival (OS), safety and tumour response. Results: A total of 110 pts with pNETs were identified. Median age was 58.0 years (range 28–89) and 52.7% were male. At baseline, 96.4% of pts had progressive disease. The Ki-67 index was ≤2% in 23.6%, 3–20% in 66.4% and &gt;20% in 2.7% of pts (7.3% missing). Metastases were present in the liver in 95.5% and bone in 29.1% of pts. Nearly all pts (90.9%) had received at least one prior anticancer therapy (somatostatin analogues: 70.0%, chemotherapy: 61.8%, protein kinase inhibitors: 38.2%). The majority of pts (70.0%) received all four scheduled cycles of 177 Lu-DOTATATE. The cumulative activity was 26.6–32.6 GBq in 65.5% of pts (&lt;26.6 GBq: 31.8%, ≥32.6 GBq: 2.7%). 12 pts were re-treated after disease progression and received 1–4 additional cycles of 177 Lu-DOTATATE. By RECIST v1.1, evaluable in 62 pts, median PFS was 24.8 months (95% CI 17.5–34.5) and objective response rate was 40.3% (95% CI 28.1–53.6); all responses were partial. The response rate, including radiological, clinical, metabolic and biomarker assessments, evaluable in 100 pts, was 54.0% (95% CI 43.7–64.0), including 2 pts with complete response. Over a median follow-up of 24.5 months (range 2.0–123.4), median OS in 110 pts was 41.4 months (95% CI 28.6–50.2). 71.8% (n=79/110) of pts had at least one treatment-emergent adverse event (TEAE). The most frequent were nausea (28.2%) and fatigue (22.7%), predominantly grade 1/2 in severity. No TEAEs led to treatment discontinuation. Grade 3 anaemia and lymphopenia occurred in 1 (0.9%) and 4 (3.6%) pts, respectively. No grade ≥3 thrombocytopenia or neutropenia were reported. Renal TEAEs occurred in 6 pts (5.5%; grade 1: n=1, grade 2: n=2, grade 3: n=3). Grade 3 renal events were transient (≤24 days) and did not lead to treatment modification. No acute leukaemia or myelodysplastic syndrome were reported within the follow-up. Conclusions: In a real-world population of pts with advanced pNETs, 177 Lu-DOTATATE was well tolerated with a safety profile consistent with the NETTER-1 trial. With limited follow-up, the OS and PFS compared favourably with cohorts of progressive pNET patients treated with other systemic agents.