On March 26, 2025, the Food and Drug Administration approved cabozantinib (Cabometyx, Exelixis, Inc.) for adult and paediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumours (pNET) and well-differentiated extra-pancreatic neuroendocrine tumours (epNET).
Efficacy of cabozantinib for patients with NETs was evaluated in CABINET (NCT03375320), a double-blind, placebo-controlled, multicentre trial with two separate, randomised cohorts (pNET and epNET) of 298 patients with unresectable, locally advanced, or metastatic pNET that had progressed on prior therapy.
In both cohorts, the major efficacy outcome measure was progression-free survival (PFS), assessed by a blinded independent radiology review committee (BIRC) per RECIST 1.1.
Additional efficacy outcome measures included overall response rate (ORR) and overall survival (OS).
The pNET cohort included 99 patients randomized (2:1) to receive cabozantinib 60 mg orally once daily or placebo until disease progression or unacceptable toxicity.
Median PFS was 13.8 months (95% 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-value <0.0001).
ORR was 18% (95% CI: 10, 30) and 0 (95% CI: 0, 11) in the respective arms.
OS data were not mature with 32 (48% of patients enrolled) deaths in the cabozantinib arm and 17 (52% of patients enrolled) 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 randomised (2:1) to receive the above regimen of 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-value <0.0001).
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 (63% of patients enrolled) deaths in the cabozantinib arm and 40 (60% of patients enrolled) 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.
The safety profile for cabozantinib was consistent with the approved product label.
The recommended cabozantinib dose for adult and paediatric patients 12 years and older with a bodyweight ≥ 40 kg is 60 mg orally once daily until disease progression or unacceptable toxicity.
The recommended dose for paediatric patients 12 years and older with a bodyweight less than 40 kg is 40 mg orally once daily until disease progression or unacceptable toxicity.
Source: FDA
