Neuroendocrine tumours

In this video, Dr Willem Lybaert, medical oncologist at the VITAZ hospital in Sint Niklaas and the University Hospital Antwerp discusses three noteworthy studies related to neuroendocrine tumours (NETs) presented during ASCO GI 2025.

In the phase III STARTER-NET trial, adding lanreotide to everolimus significantly improved the progression-free survival (PFS) of patients with unresectable or recurrent gastroenteropancreatic (GEP) NETs (grade 1/2) (median: 29.7 vs. 11.5 months; HR[99.91%CI]: 0.38[0.15-0.96]).¹ Interestingly, the study also demonstrated an overall response rate (ORR) of 23% with this combination, which is markedly better than what can be obtained with lanreotide or everolimus alone. While these findings are promising, it must be noted that this study has some important limitations. Mainly, the study lacks a comparator arm with lanreotide alone and there was no central review of the imaging in the study. Furthermore, the combination came with some bothersome everolimus-related adverse events, such as rash and fatigue. Nevertheless, the study does suggest that lanreotide-everolimus can be a first line treatment option for grade 1/2 GEP-NET patients with an aggressive disease and a contra-indication for peptide receptor radionuclide therapy (PRRT) and chemotherapy. As you can imagine, this makes up only a small proportion of patients.

In the ACTION-1 study, the first in-class alpha-emitting radiopharmaceutical therapy RYZ101 demonstrated promising antitumour activity (ORR: 29.4%) in GEP-NET patients who progressed after ¹⁷⁷Lu somatostatin analogue therapy. Furthermore, the toxicity profile of this treatment proved to be manageable, without any dose-limiting toxicities.² A phase III study with comparing this treatment to standard of care in NET patients progressing after ¹⁷⁷Lu somatostatin analogue therapy is planned. Interestingly, three Belgian centers will participate in this trial. 

A third study selected by Dr Lybaert concerned a matching adjusted indirect comparison of ¹⁷⁷Lu-DOTATE and sunitinib as first line treatment for patients with grade 2 pancreatic NETs.³ This analysis revealed a significantly better PFS for PRRT with a median of 22.8 months as compared to 11.2 months with sunitinib (HR[95%CI]:0.34[021.19-0.61]; p< 0.001).³As such, these data add to the growing body of evidence supporting PRRT as an effective first line treatment for patients with a pancreatic NET. In fact, almost simultaneously with the presentation of these data at ASCO GI, a press release of the phase III COMPETE trial was released demonstrated a superior PFS with PRRT over everolimus in the first- or second-line treatment of patients with inoperable, SSTR-positive GEP-NETs. Given the growing importance of PRRT in the treatment of NETs, Dr Lybaert underscored the importance of a good collaboration between medical oncologists and radiation specialists in the management of these patients.