FDA Officials Approve Cabozantinib for Some Patients With Pancreatic and Extra-Pancreatic Neuroendocrine Tumors

Cabozantinib (Cabometyx; Exelixis, Inc) has been approved by the FDA for use in patients aged >12 years who had previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET).¹

The approval was based on data from CABINET (NCT03375320), a double-blind, placebo-controlled, multicenter trial with 2 separate, randomized cohorts (pNET and epNET) of 298 patients with unresectable, locally advanced, or metastatic pNET that had progressed on previous therapy.

The pNET cohort included 99 patients who were randomly assigned 2:1 to receive cabozantinib 60 mg orally once daily or placebo until disease progression or unacceptable toxicity. Median progression-free survival (PFS) was 13.8 months (95% confidence interval [CI], 8.9-17.0) in the cabozantinib arm and 3.3 months (95% CI, 2.8-5.7) in the placebo arm (hazard ratio [HR] 0.22 [95% CI, 0.12-0.41]; P<.0001). The overall response rate (ORR) was 18% (95% CI, 10-30) in the cabozantinib arm and 0 (95% CI, 0-11) in the placebo arm. Overall survival data were not mature, with 32 deaths in the cabozantinib arm and 17 deaths in the placebo arm (HR 1.01 [95% CI, 0.55-1.83]). Fifty-two percent of placebo arm patients crossed over to open-label cabozantinib, which may potentially impact the evaluation of OS.

The epNET cohort included 199 patients who were randomly assigned in a 2:1 fashion to receive cabozantinib or placebo until disease progression or unacceptable toxicity. Median PFS was 8.5 months (95% CI, 6.8-12.5) in the cabozantinib arm and 4.2 months (95% CI, 3.0-5.7) in the placebo arm (HR 0.40 [95% CI, 0.26-0.61]; P<.0001). ORR was 5% (95% CI, 2.2-11) and 0 (95% CI, 0-5) in the respective arms. OS data were not mature with 83 deaths in the cabozantinib arm and 40 in the placebo arm (HR 1.05 [95% CI, 0.71-1.54]). Thirty-seven percent of those receiving placebo crossed over to open-label cabozantinib, which may potentially impact the evaluation of OS, FDA officials noted in a statement.

Reference

1. FDA. FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET. March 26, 2025. Accessed April 1, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-adults-and-pediatric-patients-12-years-age-and-older-pnet-and-epnet