FDA Approves Cabozantinib for Pancreatic and Extra-Pancreatic Neuroendocrine Tumors
Expert Perspectives · Lyn Brook · 2025-03-28
The FDA has granted approval to cabozantinib (Cabometyx®, Exelixis, Inc.) for the treatment of adult and pediatric patients aged 12 years and older with previously treated, unresectable, locally advanced, or metastatic well-differentiated pancreatic neuroendocrine tumors (pNETs) and extra-pancreatic neuroendocrine tumors (epNETs).
Why This Approval Matters
The approval of cabozantinib offers a significant advancement in the treatment of neuroendocrine tumors (NETs), a group of rare cancers that often present with limited treatment options after disease progression. By demonstrating improved progression-free survival (PFS) in both pNETs and epNETs, cabozantinib provides healthcare professionals with a validated treatment option to improve patient outcomes.
Breaking Down the CABINET Trial
The efficacy of cabozantinib was evaluated in the CABINET trial (NCT03375320), a double-blind, placebo-controlled, multicenter study. The trial included two separate randomized cohorts of patients with unresectable, locally advanced, or metastatic NETs that had progressed on prior therapy. A total of 298 patients were enrolled, with 99 in the pNET cohort and 199 in the epNET cohort. Patients within each cohort were randomized 2:1 to receive 60 mg of cabozantinib orally once daily or placebo until disease progression or unacceptable toxicity.
Key efficacy endpoints included PFS, assessed by a blinded independent radiology review committee (BIRC) per RECIST 1.1, as well as secondary endpoints including overall response rate (ORR) and overall survival (OS).
pNET Cohort Results:
- Cabozantinib demonstrated a median PFS of 13.8 months compared with 3.3 months in the placebo arm
- ORR was 18% in the cabozantinib arm versus 0% in the placebo arm
- OS data were not mature at the time of analysis, with 48% of patients in the cabozantinib arm and 52% in the placebo arm experiencing death
- Notably, 52% of placebo patients crossed over to open-label cabozantinib, potentially impacting OS evaluation
epNET Cohort Results:
- Cabozantinib achieved a median PFS of 8.5 months compared with 4.2 months in the placebo arm
- ORR was 5% in the cabozantinib arm versus 0% in the placebo arm
- OS data were immature, with 63% of patients in the cabozantinib arm and 60% in the placebo arm experiencing death
- Notably, 37% of placebo patients crossed over to open-label cabozantinib, potentially impacting OS evaluation
Managing Adverse Events
The safety profile of cabozantinib in this population was consistent with its established product label. Clinicians should monitor for known adverse events associated with cabozantinib, including gastrointestinal symptoms, hypertension, and fatigue.
Clinical Implications
“Cabozantinib, as compared with placebo, significantly improved progression-free survival in patients with previously treated, progressive, advanced extra-pancreatic or pancreatic neuroendocrine tumors,” concluded Jennifer Chan, MD, MPH, Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute, and colleagues, in their published results of the CABINET trial.
Dosing and Administration
For adult and pediatric patients aged 12 years and older with a body weight of 40 kg or more, the recommended dose is 60 mg of cabozantinib orally once daily. For pediatric patients weighing less than 40 kg, the recommended dose is 40 mg orally once daily. Treatment should continue until disease progression or unacceptable toxicity.