FDA Approval and Trial Background

On March 26, 2025, the Food and Drug Administration (FDA) approved cabozantinib for adults and pediatric patients who are 12 years and older, with pretreated unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET).

Study Design

This approval comes after the evaluation of cabozantinib for patients with NETs in the CABINET trial (NCT03375320). This double-blind, placebo-controlled, multicenter Phase III trial assessed the efficacy of cabozantinib in patients with neuroendocrine tumors (NETs). The study includes two separate randomized groups: one for pancreatic NETs (pNET) and another for extrapancreatic NETs (epNET). The trial involved 298 participants who had unresectable, locally advanced, or metastatic pNET that progressed on previous treatment.

Efficacy and Safety

The primary efficacy outcome evaluated in patients measures progression-free survival (PFS) by blinded independent central review (BICR) per RECIST 1.1. Other efficacy outcome measures included overall survival (OS) and overall response rate.

The pNET group included 99 patients, who were randomly assigned (2:1) to receive either cabozantinib 60 mg once daily or a placebo until the disease progressed or side effects became too severe. In the pNET group, below are the measured outcomes compared to the placebo group:

Median PFS:

Cabozantinib arm: 13.8 months (95% CI: 8.9, 17.0) Placebo arm: 3.3 months (95% CI: 2.8, 5.7) Hazard Ratio (HR): 0.22 (95% CI: 0.12, 0.41); p-value <0.0001

ORR:

Cabozantinib arm: 18% (95% CI: 10, 30) Placebo arm: 0% (95% CI: 0, 11)

OS data (not mature):

Cabozantinib arm: 32 deaths (48% of enrolled patients) Placebo arm: 17 deaths (52% of enrolled patients) HR: 1.01 (95% CI: 0.55, 1.83)

Notably, 52% of placebo arm patients crossed over to open-label cabozantinib, which may affect the OS evaluation.

Similarly, the epNET group consisted of 199 patients who were randomly assigned (2:1) to receive either cabozantinib or a placebo, following the same treatment plan, until the disease progressed or side effects became too severe. In the epNET group, below are the measured outcomes compared to the placebo group:

Median PFS:

Cabozantinib arm: 8.5 months (95% CI: 6.8, 12.5) Placebo arm: 4.2 months (95% CI: 3.0, 5.7) HR 0.40 (95% CI: 0.26, 0.61); p-value < 0.0001

ORR:

Cabozantinib arm: 5% (95% CI: 2.2, 11) Placebo arm: 0% (95% CI: 0, 5)

OS data(not mature):

83 deaths (63% of patients enrolled) in the cabozantinib arm 40 deaths (60% of patients enrolled) in the placebo arm HR 1.05 (95% CI: 0.71, 1.54)

Notably, 37% of placebo patients crossed over to open-label cabozantinib, potentially impacting OS evaluation.

Regarding safety, the observed adverse events were consistent with the approved product label.

The recommended dose of cabozantinib by the FDA for adults and children 12 years and older with a body weight of 40 kg or more is 60 mg taken orally once daily, until the disease progresses or side effects become too severe. For pediatric patients 12 years and older weighing less than 40 kg, the recommended dose is 40 mg taken orally once daily, until disease progression or unacceptable side effects.

About Cabozantinib

Cabozantinib is a tyrosine kinase inhibitor that targets specific tyrosine kinase receptors, which, when blocked, may slow tumor growth. In 2012, Cabozantinib was first approved in the US under the brand name Cometriq for the treatment of metastatic medullary thyroid cancer. Formulated into a capsule in 2016 as Cabometyx, cabozantinib received approval for the treatment of advanced renal cell carcinoma. The same formulation gained additional approval in the US and Canada in 2019 for previously treated hepatocellular carcinoma patients.

For further information, please refer to the clinical trial details at clinicaltrials.gov (NCT03375320) and the FDA’s official announcement.