Cabozantinib Approved for Unresectable, Advanced/Metastatic epNET and pNET

Cabozantinib yielded higher PFS in both pNET and epNET cohorts.

Cabozantinib received FDA approval for use in patients at least 12 years old with unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET) and well-differentiated extra-pancreatic neuroendocrine tumors (epNET) who have received prior treatment, according to an announcement from the FDA.¹

The efficacy of cabozantinib for these indications was established by results of CABINET(NCT03375320), a phase 3 double-blind, multicenter trial with randomized epNET and pNETcohorts with 298 patients who had unresectable, locally advanced, or metastatic disease that had progressed after previous therapy. Safety was consistent with the approved product label.

At a median follow-up of 13.9 months, patients with epNETs who received the TKI (n = 129) experienced a median progression-free survival (PFS) of 8.3 months vs 3.2 months with placebo (n = 68; stratified HR, 0.45; 95% CI, 0.30-0.66; P < .0001). At a median follow-up of 16.7 months, patients with pNETs achieved a median PFS of 11.4 months vs 3.0 months in the cabozantinib (n = 62) and placebo (n = 31) arms, respectively (stratified HR, 0.27; 95% CI, 0.14-0.49; P < .0001), according to findings presented at the 2023 European Society for Medical Oncology (ESMO) Congress.²

For patients with in the pNETs cohort, which was randomized 2:1 for patients to receive 60 mg of cabozantinib 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 <0.0001). Likewise, objective response rate (ORR) was 18% (95% CI, 10-30) and 0 (95% CI, 0-11) in the respective arms.¹

In the placebo arm, 52% of patients crossed over to open-label cabozantinib, which may affect overall survival (OS) data, which were not mature at the time of study, with 32 and 17 deaths in the cabozantinib and placebo arms, respectively (HR, 1.01; 95% CI, 0.55-1.83).¹

This was true of the epNET cohort as well, where 83 and 40 deaths occurred in respective arms (HR, 1.05; 95% CI, 0.71-1.54) and 37% of the placebo arms crossed over to open-label cabozantinib.¹

For patients with in the epNETs cohort, which was also randomized 2:1 for patients to receive the aforementioned cabozantinib regimen or placebo until 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 <0.0001). ORR was 5% (95% CI, 2.2-11) and 0 (95% CI, 0-5) in the respective arms.¹

For patients with a body weight of at least 40 kg, the recommended dose is 60 mg orally once daily until disease progression or unacceptable toxicity. The recommended dose for those with a body weight less than 40 kg is 40 mg daily until progression or unacceptable toxicity.¹

Reference

1. FDA approves cabozantinib for adults and pediatric patients 12 years of age and older with pNET and epNET. FDA. March 26, 2025. Accessed March 26, 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?utm_medium=email&utm_source=govdelivery
2. Chan J, Geyer S, Ou FS, et al. Alliance A021602: Phase III, double-blinded study of cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET). Ann Oncol. 2023;34(suppl 2):S192. doi:10.1016/j.annonc.2023.10.047