ENETS 2025 – Daily Highlights 2

In this daily highlights video, Dr Willem Lybaert, medical oncologist at VITAZ and the University Hospital Antwerp and coordinator of the NETwerk ENETS center of excellence, discusses some of his key take-aways form ENETS 2025.

A first abstract discusses a subgroup analysis of the randomized, phase III CABINET trial zooming in on patients with grade 3 neuroendocrine tumors (NETs). Last year, results of the CABINET trial showed that cabozantinib significantly improves the progression-free survival (PFS) of patients with previously treated, progressive advanced extra pancreatic (ep) or pancreatic (p) NETs compared to placebo. The subgroup analysis presented at ENETS 2025 included 24 patients with a grade 3 NET. As expected, the primary tumor site was pancreatic in most of these patients (50%), but the analysis also included 2 patients with a lung or thymus NET. Patients in the study received a median of 2 prior treatment lines (range:1-7). In line with the overall results of CABINET, cabozantinib proved to be associated with a significantly longer PFS than placebo in grade 3 patients (median: 7.9 vs. 3.0 months; HR[95%CI]: 0.15[0.04-0.57]). This benefit was most pronounced in pNET patients, where the median PFS was reported at 13.5 months with cabozantinib as compared to 1.5 months with placebo. Among epNET patients, these medians were reported at 6.5 and 4.2 months, respectively. The objective response rate (ORR) with cabozantinib in grade 3 patients was 25%. As such, these findings further support the use of cabozantinib in previously treated NET patients, irrespective of the tumor grade.

Similar to the randomized phase III STARTER-NET study, the phase II LOLA trial evaluates a combination of a tyrosine kinase inhibitor (TKI) and a somatostatin analogue (SSA) in patients with a well-differentiated, grade 2 NET (pancreatic and/or carcinoid K67 ≥10%). During ENETS 2025, results of the run-in phase of this trial were presented showing the feasibility of using a combination of cabozantinib and an SSA in this setting. Importantly, however, the cabozantinib dose had to be reduced in 50% of the patients. Efficacy results of this trial are eagerly awaited.²

In the final part of the video, Dr Lybaert turns the attention to different SSA formulations. In this light, the BACKSOM study is currently evaluating the experiences of NET patients who were initially treated with a prefilled syringe of lanreotide autogel and switch to a generic SSA formulation that uses a syringe that requires assembly. The study will also assess the reasons for this switch and will investigate the characteristics of patients who switch back to the prefilled syringe.³ Studies like this, looking at patient experience and quality of life, are especially relevant given the long treatment duration with SSA in NET patients. In addition to these different syringes, studies are also ongoing evaluating the safety and efficacy of oral SSA formulations. In this respect, promising safety data have been generated with paltusotine in the treatment of patients with carcinoid syndrome.