Dr Trikalinos on Cabozantinib in Functional and Nonfunctional NETs

Nikolaos Trikalinos, MD, discusses findings from a post hoc analysis of the CABINET trial evaluating cabozantinib (Cabometyx) in patients with functional and nonfunctional neuroendocrine neoplasms. In this interview from the 2026 North American Neuroendocrine Tumor Society (NANETS) Symposium, he explains that the analysis showed that cabozantinib had a favorable effect on progression-free survival (PFS) in both subgroups, with no additional grade 3 adverse events identified in these patients.

Trikalinos, of Washington University in St. Louis, explains that functional and nonfunctional neuroendocrine tumors are completely different diseases with different disease trajectories. Patients with functional tumors commonly experience diarrhea and flushing and are generally in worse shape. That raised two questions going into the analysis. The first was whether treating these patients with an agent that carries its own side effects might lead to more toxicity. The second was whether, because these are distinct diseases, cabozantinib might have a differential effect depending on functional status.

According to Trikalinos, the data showed a PFS benefit with cabozantinib for both functional and nonfunctional tumors. In the nonfunctional subgroup, the hazard ratio was 0.26, and that result remained statistically significant after adjusting for tumor origin, ECOG performance status, and tumor grade. He notes that cabozantinib is useful in patients with both functional and nonfunctional disease.

The investigators also looked at whether cabozantinib adds significantly to the side effect profile, specifically whether it increases diarrhea, fatigue, or liver function abnormalities in patients who, as Trikalinos puts it, come preloaded with those symptoms, particularly those with functional tumors. No additional grade 3 side effects were found. Analyses are ongoing, including biomarker work, but so far there is no additional safety signal associated with cabozantinib use.

Trikalinos explains that cabozantinib’s side effect profile reflects VEGF inhibition and includes hypertension, mouth problems, diarrhea, and fatigue, effects that have been well described in neuroendocrine tumors and across many other patient populations. On dosing, he says the 60 mg starting dose used on trial should be attempted, but dose reductions are nothing to feel bad about. In his view, 40 mg appears to be a quite acceptable dose, and the trial allowed for a dose as low as 20 mg daily. He also points to a current trial comparing 40 mg and 60 mg in terms of efficacy and tolerance, which he says merits consideration.