FDA

Cabometyx OK'd for advanced neuroendocrine tumors

March 28, 2025

FDA approved Cabometyx (cabozantinib) for the treatment of:

1) adult and pediatric patients ≥12 years of age with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET); and

2) adult and pediatric patients ≥12 years of age with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic NET (epNET).

Efficacy

Approval for the new indication was based on data from the phase 3 CABINET trial (NCT03375320) involving 298 patients (pNET: n = 99; epNET: n = 199) who were randomly assigned 2:1 to receive cabozantinib 60mg PO once daily or placebo until disease progression or unacceptable toxicity. Patients randomized to placebo were allowed to crossover to Cabometyx upon confirmation of progressive disease. The major efficacy outcome was progression free survival (PFS) assessed by a blinded real-time central review.

pNET cohort:

Cabozantinib statistically significantly improved PFS compared with placebo (median PFS: 13.8 months [95% confidence interval [CI], 8.9-17.0] vs. 3.3 months [95% CI, 2.8-5.7]; hazard ratio [HR], 0.22 [95% CI, 0.12-0.41]; P <0.0001). Overall response rate (ORR) was 18% (95% CI, 10-30) with cabozantinib and 0% (95% CI, 0-11) with placebo. Duration of response (DOR) was 11.4 months (95% CI, 6.1, not evaluable) in the cabozantinib group and not evaluable in the placebo group.

Overall survival (OS) data weren’t mature. At the time of analysis, there were 32 deaths (48%) in the cabozantinib arm and 17 deaths (52%) in the placebo arm (HR, 1.01 [95% CI, 0.55-1.83]). The rate of cross-over of placebo patients to open-label cabozantinib was 52%.

epNET cohort:

Cabozantinib resulted in a statistically significant improvement in PFS compared with placebo (median PFS: 8.5 months [95% CI, 6.8-12.5] vs. 4.2 months [95% CI, 3.0-5.7]; HR, 0.40 [95% CI, 0.26-0.61]; P <0.0001). ORR was 5% (95% CI, 2.2-11) with cabozantinib and 0% (95% CI, 0-5) with placebo. DOR was 8.3 months (95% CI, 4.5, not evaluable) in the cabozantinib group and not evaluable in the placebo group.

OS data weren’t mature at the time of analysis. There were 83 (63%) deaths in the cabozantinib arm and 40 (60%) deaths in the placebo arm (HR, 1.05 [95% CI, 0.71-1.54]). The rate of cross-over of placebo patients to open-label cabozantinib was 37%.

Safety

The safety profile of cabozantinib observed in each CABINET cohort was consistent with its known safety profile. No new safety signals were identified; however, the incidence of hypertension, regardless of treatment arm, was higher in NET patients compared with other approved tumor types, according to the manufacturer press release.

Sources:

Cabometyx (cabozantinib) [package insert]. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/208692s017lbl.pdf Revised March 2025. Accessed March 27, 2025.

FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET. [News release]. 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

Exelixis announces US FDA approval of Cabometyx® (cabozantinib) for patients with previously treated advanced neuroendocrine tumors. [News release]. 2025. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-us-fda-approval-cabometyxr-cabozantinib-4