Multicenter phase 3 trial of cabozantinib for previously treated advanced neuroendocrine tumors

There are limited treatment options for patiens with advanced neuroendocrine tumors. The multicenter phase 3 CABINET trial in the United States evaluated cabozantinib for previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors. Patients were recruited in two independent cohorts – those with extrapancreatic neuroendocrine tumors (n=203) and those with pancreatic neuroendocrine tumors (n=95). Patients were randomized 2:1 to cabozantinib 60 mg once daily or placebo. The primary endpoint was progression-free survival as assessed by blinded independent central review. In the extrapancreatic neuroeondocrine tumor cohort, the median PFS was 13,8 months with cabozantinib versus 3.9 months with placebo (sHR 0.38; p<0.001), whereas in the pancreatic endocrine tumor cohort, the median PFS was 13.8 months with cabozantinib versus 4.4 months with placebo (sHR 0.23; p<0.001). The incidence of confirmed objective response with cabozantinib was 5% and 19% among patients with extrapancreatic and pancreatic neuroendocrine tumors, respectively, as compared with 0% with placebo. Adverse events were consistent with the known safety profile of cabozantinib. The authors conclude that cabozantinib, as compared with placebo, significantly improved progression-free survival among patients with previously treated, progressive advanced extrapancreatic or pancreatic neuroendocrine tumors.