Cabozantinib is approved by the USFDA for adults and pediatric patients 12 years of age and older with pNET and epNET

On March 26, 2025, the Food and Drug Administration sanctioned cabozantinib (Cabometyx, Exelixis, Inc.) for adult and pediatric patients aged 12 and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET).

The efficacy of cabozantinib for patients with neuroendocrine tumors (NETs) was assessed in the CABINET trial (NCT03375320), a double-blind, placebo-controlled, multicenter study comprising two distinct randomized cohorts (pNET and epNET) involving 298 patients with unresectable, locally advanced, or metastatic pNET that had progressed following prior treatment.

In both groups, the main measure of effectiveness was progression-free survival (PFS), which was assessed by a blind review committee of radiologists following RECIST 1.1 guidelines. Additional measures of effectiveness included overall response rate (ORR) and overall survival (OS). Supplementary efficacy outcome variables were overall response rate (ORR) and overall survival (OS).

The pNET group comprised 99 patients randomized in a 2:1 ratio to receive cabozantinib 60 mg orally once day or a placebo until disease progression or intolerable toxicity occurred. The median progression-free survival (PFS) was 13.8 months (95% confidence interval [CI]: 8.9, 17.0) for the cabozantinib group and 3.3 months (95% CI: 2.8, 5.7) for the placebo group, with a hazard ratio (HR) of 0.22 (95% CI: 0.12, 0.41; p-value <0.0001).

The overall response rate (ORR) was 18% (95% confidence interval: 10, 30) and 0% (95% confidence interval: 0, 11) in the corresponding groups. The overall survival data was not complete, with 32 deaths (48% of the patients) in the cabozantinib group and 17 deaths (52% of the patients) in the placebo group (HR 1.01 [95% CI: 0.55, 1.83]). Fifty-two percent of patients in the placebo group transitioned to open-label cabozantinib, which may influence the assessment of overall survival.

The epNET cohort had 199 patients randomized in a 2:1 ratio to receive either cabozantinib or placebo until disease progression or intolerable toxicity occurred. The median progression-free survival (PFS) was 8.5 months (95% CI: 6.8, 12.5) for the cabozantinib group and 4.2 months (95% CI: 3.0, 5.7) for the placebo group (hazard ratio 0.40 [95% CI: 0.26, 0.61]; p-value <0.0001).

The overall response rate (ORR) was 5% (95% confidence interval: 2.2, 11) and 0% (95% confidence interval: 0, 5) in the corresponding groups. The overall survival data was not complete, with 83 deaths (63% of the patients who received cabozantinib) and 40 deaths (60% of the patients who received the placebo) (HR 1.05 [95% CI: 0.71, 1.54]). Thirty-seven percent of those receiving placebo transitioned to open-label cabozantinib, which may influence the assessment of overall survival.

The safety profile of cabozantinib aligned with the approved product label.

Adult and pediatric patients aged 12 years and older with a body weight of at least 40 kg are advised to take a 60 mg dosage of cabozantinib orally once a day until disease progression or intolerable toxicity occurs. The advised dosage for pediatric patients aged 12 years and older weighing less than 40 kg is 40 mg administered orally once daily until illness progression or intolerable toxicity occurs.

This evaluation was performed under Project Orbis, a program of the FDA Oncology Center of Excellence. Project Orbis offers a framework for the simultaneous submission and evaluation of oncology treatments among global collaborators. For this review, the FDA partnered with the Australian Therapeutic Goods Administration (TGA) and Switzerland’s Swissmedic. The application evaluations are currently in progress at the other regulatory bodies.