The CABINET trial

Prof Dr Timon van Damme, digestive oncologist at the University Hospital of Antwerp and Head of Network of the ENETS Centre of Excellence in the Antwerp-Waasland region discusses the results of the CABINET trial, which were published in February 2025 in the New England Journal of Medicine. These findings are significant, impactful, and will likely change how patients with neuroendocrine tumours (NETs) will be treated.

The trial evaluated the efficacy of cabozantinib in patients with either extra-pancreatic NETs or pancreatic NETs. Patients were randomized in a 2:1 ratio to receive either 60 mg of cabozantinib daily until disease progression or a placebo until progression. Those in the placebo group were allowed to cross over to receive cabozantinib upon progression. The primary endpoint was PFS, assessed by blinded, independent central review. Secondary endpoints included OS, ORR, safety, and tolerability.

In the extra-pancreatic NET cohort, approximately 190 patients participated. This group included a mix of grade 1 to grade 3 NETs, with gastrointestinal and lung NETs, the latter accounting for about 20% of the cohort. These were heavily pretreated patients, having undergone a median of two prior systemic therapies, with a range from one to seven previous treatments. In the pancreatic NET cohort, 90 patients were enrolled, also spanning grades 1 to 3 and having received a median of three prior therapies, ranging from one to nine previous treatments.

The trial met its primary endpoint, showing a significant improvement in median PFS in both cohorts. In extra- pancreatic NETs, median PFS was 8.4 months with cabozantinib, compared to 3.9 months with placebo. In pancreatic NETs, cabozantinib led to a median PFS of 13.8 months, compared to just 4.4 months in the placebo group. These results demonstrate a clear benefit of cabozantinib in delaying disease progression.

In terms of overall survival, no statistically significant differences were observed between the treatment and placebo groups in either cohort. However, in pancreatic NETs, there was a numerically notable difference, with cabozantinib showing a median OS of 14 months compared to 31 months in the placebo arm. The absence of a statistically significant OS difference is likely due to the crossover design of the study, allowing patients in the placebo group to receive cabozantinib upon progression.

Objective response rates varied between the two cohorts. In extra-pancreatic NETs, the ORR was relatively low, around 4%, suggesting limited tumour shrinkage. In contrast, in pancreatic NETs, the ORR was higher at approximately 18%, indicating a more pronounced tumour response to treatment.

Like any treatment, cabozantinib is associated with side effects. Notable adverse events observed in the trial included fatigue, diarrhoea, changes in liver function, and hypertension. These side effects are manageable but require careful monitoring when prescribing cabozantinib to patients.

Cabozantinib has demonstrated a clear benefit in prolonging PFS in heavily pretreated NET patients, including those with gastrointestinal, pancreatic, and lung NETs across all tumour grades. The relatively high response rate in pancreatic NETs further highlights its potential as an effective treatment option. While side effects need to be managed, the overall benefit of cabozantinib makes it a valuable new option for patients with previously treated NETs.