The CABINET study: cabozantinib for progressive NET

Previously, the randomized phase III CABINET study demonstrated a significant improvement in progression-free survival (PFS) with cabozantinib vs. placebo in the treatment of patients with previously treated, progressive advanced extra-pancreatic or pancreatic neuroendocrine tumours (NETs). In this video, Dr Willem Lybaert (VITAZ & University Hospital Antwerp, Sint-Niklaas & Antwerp, Belgium) discusses the updated, final PFS results of this trail with Dr Jennifer Chan, medical oncologist at the Dana Farber Cancer Institute in Boston (MA, USA) and principal investigator of the CABINET trial.

CABINET enrolled patients in two independent cohorts: those with extra-pancreatic NETs and those with pancreatic NETs. To be eligible for the study, patients had to be pretreated with peptide receptor radionuclide therapy (PRRT), targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo.

In the extra-pancreatic cohort, cabozantinib was associated with a median PFS of 8.4 months as compared to 3.9 months with placebo. This corresponds to a significant 62% lower risk of disease progression or death for patients treated with cabozantinib (HR[95%CI]: 0.38[0.25-0.59]; p< 0.0001). Cabozantinib also significantly improved the PFS in the pancreatic cohort with a median PFS of 13.8 months as compared to 4.4 months with placebo (HR[95%CI]: 0.23[0.12-0.42]; p< 0.0001). Importantly, the PFS benefit obtained with cabozantinib was seen irrespective of the level of differentiation, the tumour grade, the primary tumour site (for extra-pancreatic NETs) and the type of prior therapy.

The benefit in PFS observed with cabozantinib did come at the cost of additional toxicity, with an incidence of grade 3-4 adverse events in patients treated with cabozantinib of 62%-65% as compared to 23-27% in the placebo arm. A closer look at the treatment exposure for patients in the study learned that the average daily dose of cabozantinib was only about 38 mg, which is markedly lower than the 60 mg stipulated in the protocol. In fact, 66-68% of patients required a dose reduction, mainly because of tolerability issues. Despite this finding, Dr Chan would not argue to start treatment with a lower dose. Instead, she recommends to start with the 60 mg dose but have a low threshold to reduce the dose in case of tolerability issues.

In conclusion, the final PFS results of CABINET identify cabozantinib as an effective treatment option for previously treated pancreatic or extra-pancreatic NETs, irrespective of tumour grade, differentiation, tumour location and prior therapy.