Mini oral session – neuroendocrine tumors

At the ESMO 2025 mini oral session on neuroendocrine tumors (NETs), seven presentations provided new insights into both radioligand-based and alternative therapeutic strategies. In this video, Prof Timon Vandamme, digestive and NET oncologist at the Antwerp University Hospital shares his key takeaways from this session.

Not surprisingly, a central focus of the mini oral session on NETs was peptide receptor radionuclide therapy (PRRT), with three abstracts addressing advances in this field. The first presented data on 212Pb-VMT-α,NET, an alpha-emitting PRRT evaluated in a safety and dose-finding study. Encouragingly, no dose-limiting toxicities or unexpected safety concerns were observed, reaffirming the generally favorable safety profile of PRRT.¹ A second abstract reported the two-year outcomes from the phase II, ALPHAMEDIX 02 trial investigating 212Pb-DOTAMTATE. This study demonstrated an overall response rate of 60%, with a duration of response rate at 24 months of 71.9%.² These findings indicate that alpha-emitting PRRT may confer meaningful and lasting benefit in patients with NETs. The third PRRT-related presentation described a phase I trial of beta-emitting PRRT in combination with triapine, a drug designed to potentiate the efficacy of radionuclide therapy. Early results indicated promising activity without additional safety concerns. Further evaluation is ongoing in the United States to determine the clinical efficacy of this strategy.³

Beyond radioligand approaches, three abstracts highlighted novel systemic treatment strategies. The LIGHTSPARK-015 trial investigated belzutifan, a HIF-2α inhibitor with known activity in von Hippel–Lindau (VHL)-driven tumors, in patients with pancreatic NETs. In this setting, however, belzutifan demonstrated limited activity with few objective responses (ORR: 10%), suggesting that further development in pancreatic NETs may not be warranted.⁴

 Two early-phase Chinese studies evaluated bispecific antibodies in aggressive neuroendocrine carcinomas. ZG005, a bispecific antibody targeting PD-1 and TIGIT, was tested in combination with platinum–etoposide chemotherapy in the first-line setting. The study reported an objective response rate of ~50% with no significant new toxicities, supporting the potential role of dual checkpoint inhibition in this context.⁵ Another compound, ZG006, a bispecific T-cell engager targeting DLL3, showed activity in monotherapy with an ORR of approximately 40%. While low-grade cytokine release syndrome was observed, the overall safety profile of this agent was manageable. The efficacy signal observed in this study was encouraging for this aggressive tumor type and warrant further clinical evaluation.⁶

The final abstract addressed supportive care describing a tool developed by the Spanish Neuroendocrine Tumor Society (GETNE) to screen for malnutrition in NET patients. The study underscored the high prevalence of malnutrition in this population and highlighted the clinical relevance of systematic nutritional assessment as part of comprehensive care.⁷