FDA Approves Cabozantinib for Patients With Locally Advanced or Metastatic Well-Differentiated pNETs and epNETs

On March 26th, 2025, the US Food and Drug Administration (FDA) approved cabozantinib for patients 12 years of age and older with unresectable locally advanced or metastatic well-differentiated pancreatic neuroendocrine tumors (pNETs) and well-differentiated extra-pancreatic neuroendocrine tumors (epNETs) who experienced disease progression after prior therapy. This approval was based on results from the CABINET trial. 

In this double-blind, placebo-controlled trial, researchers enrolled 298 patients with unresectable locally advanced or metastatic well-differentiated pNETs (n = 99) and epNETs (n = 199). Patients were distributed into cohorts based on disease type and randomized on a 2-to-1 basis to receive either 60 mg of cabozantinib or placebo once daily until disease progression or unacceptable toxicity.  The primary end point was progression-free survival (PFS). Key secondary end points included overall response rate (ORR) and overall survival (OS). 

At analysis in the pNETs cohort, median PFS was 13.8 months in the cabozantinib arm and 3.3 months in the placebo arm (hazard ratio [HR] 0.22; 95% confidence interval [CI], 0.12 to 0.41; P < .0001). The ORR was 18% and 0%, respectively. OS data was not yet mature, with 32 deaths in the cabozantinib arm and 17 deaths in the placebo arm. Seventeen patients in the placebo arm crossed over to the cabozantinib arm. 

At analysis in the epNETs cohort, median PFS was 8.5 months in the cabozantinib arm and 4.2 months in the placebo arm (HR 0.40; 95% CI, 0.26 to 0.61; P < .0001). The ORR was 5% and 0%, respectively. OS data was not yet mature with 83 deaths in the cabozantinib arm and 40 deaths in the placebo arm. Seventy-four patients in the placebo arm crossed over to the cabozantinib arm. 

The recommended cabozantinib dose for patients 12 years and older with a bodyweight ≥ 40 kg is 60 mg once daily until disease progression or unacceptable toxicity. The recommended cabozantinib dose for patients with a body weight < 40 kg is 40 mg once daily until disease progression or unacceptable toxicity. 

Source: 

FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET. Accessed on March 26, 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