ENETS 2025 – Daily Highlights 1

In this daily highlights video, Prof Dr Timon Vandamme, digestive oncologist at the University Hospital Antwerp and coordinator of the NETwerk ENETS center of excellence, discusses two groundbreaking studies presented during ENETS 2025.

COMPETE is a prospective, randomized, controlled, open-label, phase 3 trial that enrolled 309 patients with inoperable, progressive, grade 1 or 2 (Ki-67 ≤20%) somatostatin receptor (SSTR)-positive neuroendocrine tumors of gastroenteric or pancreatic origin (GEP-NET). Patients in the study were randomized (2:1) to receive ¹⁷⁷Lu-edotreotide every three months for up to four cycles, or everolimus 10 mg daily for up to 30 months, or until disease progression.. Patients were stratified according to the primary tumour origin and the prior use of a somatostatin analogue (SSA) (1^st vs. 2^nd line). The two arms in the study were well balanced with approximately 85% of patients being previously treated with a SSA. The study convincingly met its primary endpoint by showing a significantly longer median progression-free survival (PFS) for ¹⁷⁷Lu-edotreotide compared to everolimus (median: 23.9 vs. 14.1 months; HR[95%CI]: 0.67[0.48-0.95]; p= 0.022). Data for OS were immature, but for the moment no OS benefit was observed. Safety was in line with what could be expected, with the ¹⁷⁷Lu-edotreotide treatment being associated with a treatment-related adverse event rate of 30.4% as compared to 44.4% in the everolimus arm. For Prof Vandamme, these data identify peptide receptor radionuclide therapy (PRRT) as a new standard of care for patients with grade 1/2 SSTR-positive GEP-NET who progress following a treatment with a SSA.¹

ENETS 2025 also featured the presentation of the secondary endpoints of the OCLURANDOM trial. In this study, 84 patients with unresectable malignant pancreatic NETs who received 1 prior line of cytotoxic chemotherapy were randomly assigned to receive ¹⁷⁷Lu-Dota-Octreotate (7.4 GBq per injection with a maximum of 4 injections), or sunitinib (37.5 mg QD). Patients who previously received a TKI, or PRRT were excluded from the study. Previous reports of this study showed a significantly higher 12-month PFS rate among patients treated with ¹⁷⁷Lu-Dota-Octreotate compared to sunitinib (80.5% vs. 41.9%). From the presentation at ENETS 2025 it became clear that the PFS benefit obtained with ¹⁷⁷Lu-Dota-Octreotate did not translate into a benefit in OS, with a median of 55.8 months for ¹⁷⁷Lu-Dota-Octreotate as compared to 64.4 months with sunitinib. For Prof Vandamme, this lack of an OS benefit did not come as a surprise given the high rate of cross-over from the control arm to PRRT in this study. The updated results of OCLURANDOM did show an impressive benefit in ORR for ¹⁷⁷Lu-Dota-Octreotate compared to sunitinib with an ORR of 63% and 28%, respectively. The fact that ¹⁷⁷Lu-Dota-Octreotate induces a response in almost two thirds of patients is an unprecedented finding in the context of pancreatic NETs and truly underscores the potential of this treatment modality to reduce tumor volumes. Also in terms of safety ¹⁷⁷Lu-Dota-Octreotate outperformed sunitinib, with 56% of patients in the ¹⁷⁷Lu-Dota-Octreotate arm reporting to be free from all side effects at week 36 as compared to 13% in the sunitinib arm.²

Apart from these two pivotal studies, ENETS 2025 also included some interesting abstracts addressing the use of liquid biopsies in patients with NETs. In this respect Laura Mariën was awarded with a poster award for her poster discussing the NET-IMPRESS assay, a methylation-based assay that can be used to diagnose and monitor NET patients using liquid biopsies.³