Cabozantinib shows clinically meaningful improvement in advanced neuroendocrine tumours

Dr Jennifer Chan – Dana-Farber Cancer Institute, Boston, USA

The CABINET trial is a phase III double-blinded study of cabozantinib versus placebo in patients with advanced extra-pancreatic and pancreatic NET. The trial was specifically designed to evaluate the efficacy of cabozantinib in patients who had received prior therapy. It is a phase III trial; there are two cohorts of patients: the first one is patients with epNET and the second one is patients with pNET or pancreatic NET. Each of the cohorts had an independent statistical design and analysis plan. Patients were randomised 2:1 to receive cabozantinib, starting at a dose of 60mg daily, or placebo. The primary endpoint of the study was progression free survival. We had secondary endpoints including response rate, overall survival and safety and tolerability.

At the end of July this year the DSMB voted to stop the study early based on the efficacy that was seen in the interim analysis for both of these cohorts. It was the second interim analysis for patients with epNET and the first interim analysis for patients with pNET. What we observed in all of the patients that were enrolled during 2023 in the epNET cohort was an improvement in the median progression free survival from 8.3…. What we observed in the epNET cohort was an improvement in progression free survival. Patients receiving cabozantinib had a median progression free survival of 8.3 months compared to 3.2 months in patients receiving placebo. This was a hazard ratio of 0.45 in favour of cabozantinib.  In the pNET cohort there was also an improvement in progression free survival. The median PFS for patients getting cabozanitinib was 11.4 months compared to 3.0 months for patients receiving placebo.

As we looked at adverse events we didn’t notice any new safety signals with cabozantinib in the patients that were treated. The adverse events that we observed were consistent with the known safety profile of cabozantinib. With respect to response rate, in the epNET cohort we saw a response rate of 4% in patients receiving cabozantinib compared to 1% in patients receiving placebo. In the pNET cohort the response rate was 18% compared to 6% of patients receiving placebo. We have not yet observed any overall survival differences but I anticipate the results are going to be impacted by crossover from placebo to cabozantinib and potentially also subsequent lines of therapy.

So we, in summary, found an improvement in progression free survival for patients receiving cabozantinib in both the extra-pancreatic NET cohort and the pancreatic NET cohort. We did not observe any new safety signals. Based on our results we think that cabozantinib may be a new treatment option for patients with previously treated NETs.