Cabozantinib Secures EU Approval for Advanced Neuroendocrine Tumors

On July 24, 2025, the European Commission (EC) granted approval to cabozantinib (brand name: Cabometyx) for the treatment of adult patients with unresectable or metastatic neuroendocrine tumors (NETs), specifically pancreatic (pNET) and extra-pancreatic (epNET) variants, who have previously undergone at least one systemic therapy not involving somatostatin analogues. This significant regulatory decision marks cabozantinib as the first systemic therapy authorized in the European Union for patients with advanced NETs, regardless of tumor site or grade.

The approval was primarily supported by data from the pivotal phase 3 CABINET trial (NCT03375320), which presented substantial evidence of cabozantinib's efficacy. According to results revealed at the 2024 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine, cabozantinib demonstrated a 77% reduction in disease progression risk among pNET patients and a 62% reduction in the epNET cohort compared to placebo. Specifically, the median progression-free survival (PFS) was reported as 13.8 months for pNET patients versus 4.4 months for those receiving placebo, and 8.4 months for epNET patients compared to 3.9 months for placebo recipients.

Dr. Sandra Silvestri, MD, PhD, Chief Medical Officer at Ipsen, expressed optimism regarding the approval, stating, "The complex nature of NETs and lack of innovation in recent years has resulted in significant physical and emotional strain for patients as their disease progresses. This approval offers a unique, simplified, and efficacious treatment option upon progression, where few to no other options currently exist."

The CABINET trial was a double-blinded, placebo-controlled study assessing the efficacy and safety of cabozantinib among 298 enrolled patients with previously treated, locally advanced or metastatic NETs. The trial highlighted the agent's safety profile, noting that common adverse effects included hypertension, fatigue, and diarrhea, with grade 3 or higher adverse events occurring in 62% to 65% of cabozantinib-treated patients versus 23% to 27% in the placebo group.

Dr. Marianne Pavel, an endocrinologist and NET expert at Friedrich-Alexander University of Erlangen, emphasized the advancements made through the CABINET study, stating, "The number of available therapies is limited, and not all patients with NET may benefit from currently approved therapies. Advancements like those achieved through the CABINET study are offering new treatment opportunities to delay disease progression in patients with well-differentiated NET, irrespective of the type of NET."

This recent approval follows the March 2025 FDA endorsement of cabozantinib for both adult and pediatric patients aged 12 years and older with previously treated, unresectable, locally advanced or metastatic pNET and epNET. The growing body of evidence supporting cabozantinib’s efficacy underscores a crucial development in oncology, particularly for patients facing limited treatment options.

In conclusion, cabozantinib's approval represents a significant milestone in the management of advanced neuroendocrine tumors, providing hope for improved patient outcomes and paving the way for further advancements in therapeutic options for this challenging group of cancers.