FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET

Regulatory approval: On March 26, 2025, the FDA approved cabozantinib (Cabometyx) for adult and pediatric patients aged ≥12 years with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic NET (pNET) and well-differentiated extra-pancreatic NET (epNET). Approval was supported by the randomized, double-blind CABINET trial, which showed improved BIRC-assessed PFS vs placebo in both pNET and epNET cohorts; OS data were not mature and crossover may affect OS interpretation.

FDA approval (Mar 26, 2025): cabozantinib for pNET and epNET

The US FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) on March 26, 2025 for adult and pediatric patients ≥12 years with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET).

Evidence base: CABINET (NCT03375320)

CABINET was a double-blind, placebo-controlled, multicenter trial with two randomized cohorts (pNET and epNET). The major efficacy endpoint in both cohorts was PFS by BIRC per RECIST 1.1; additional endpoints included ORR and OS.

  • pNET cohort (n=99; 2:1 randomization): median PFS 13.8 mo with cabozantinib vs 3.3 mo with placebo (HR 0.22; p<0.0001). ORR 18% vs 0%. OS not mature (HR 1.01); 52% of placebo patients crossed over, which may affect OS evaluation.
  • epNET cohort (n=199; 2:1 randomization): median PFS 8.5 mo vs 4.2 mo (HR 0.40; p<0.0001). ORR 5% vs 0%. OS not mature (HR 1.05); 37% crossover from placebo.

Dosing and review notes

Recommended dose: 60 mg once daily for adults and pediatric patients ≥40 kg; 40 mg once daily for pediatric patients <40 kg, until progression or unacceptable toxicity. Safety was reported as consistent with the existing product label. Review was conducted under Project Orbis; other agencies’ reviews were ongoing.

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