Cabozantinib Gains FDA Approval for Patients With Pancreatic Neuroendocrine Tumors

Cabozantinib (Cabometyx; Exelixis, Inc) received FDA approval for adult and pediatric patients 12 years of age 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 decision is based on data from the randomized, double-blind, placebo-controlled, multicenter CABINET trial (NCT03375320).¹

3D illustration of pancreatic cancer cells | Image Credit: © Dassen - stock.adobe.com

PNET is a rare type of cancer that begins in the pancreas and is characterized by the development of tumors from islet cells, which produce hormones. Some pancreatic cancers produce too many hormones and are called functional tumors; however, most pNET cancers do not produce excessive hormones and are considered nonfunctional tumors. Similar to other cancer types, pNET treatment options have greatly expanded to include targeted therapies alongside traditional radiotherapy or chemotherapy.²

Patients with pNET have more favorable prognoses with a 5-year survival rate of 95% for localized disease. Despite this promising statistic, patients with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET need advanced options. Cabozantinib is a tyrosine kinase inhibitor with multiple approved indications for various cancers, including RCC, thyroid cancer, and hepatocellular carcinoma. In 2017, it received approval as a monotherapy for the treatment of patients with advanced RCC, which was followed by an additional approval for its use in combination with nivolumab (Opdivo, Bristol-Myers Squibb Co). In the CABINET trial, the agent demonstrated its promising potential for patients with pNET or epNET.^3-5

The trial included 298 participants with unresectable, locally advanced, or metastatic pNET that had progressed on prior therapy who were separated into 2 randomized cohorts: the pNET cohort (n = 99) and epNET cohort (n = 199). Both cohorts were randomized 2:1 to receive either cabozantinib 60 mg orally once daily or placebo until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS), as well as secondary end points including overall response rate (ORR) and overall survival (OS).⁵

In the pNET cohort, the 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 < .0001). Patients receiving cabozantinib achieved an ORR of 18% (95% CI: 10, 30) compared with 0% (95% CI: 0, 11), respectively.⁵

The OS data are immature. In the cabozantinib arm of the pNET cohort, 32 patients died compared with 17 in the placebo arm (HR 1.01 [95% CI: 0.55, 1.83]). In the placebo arm, 52% of patients crossed over to open-label cabozantinib.⁵

In the epNET cohort, the cabozantinib arm achieved a median PFS of 8.5 months (95% CI: 6.8, 12.5), whereas the placebo arm was 4.2 months (95% CI: 3.0, 5.7; HR 0.40 [95% CI: 0.26, 0.61]; P < .0001). In each arm, the ORR was 5% (95% CI: 2.2, 11) and 0% (95% CI: 0, 5), respectively. With 40 fatalities (60% of patients enrolled) in the placebo arm and 83 deaths (63% of patients enrolled) in the cabozantinib arm (HR 1.05 [95% CI: 0.71, 1.54]), the OS results were not mature. The assessment of OS may be impacted by the fact that 37% of patients who received a placebo switched to open-label cabozantinib.⁵

The safety profile was favorable and consistent with the approved product label.⁵

The recommended cabozantinib dose for adult and pediatric 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 pediatric patients 12 years and older with a bodyweight less than 40 kg is 40 mg orally once daily until disease progression or unacceptable toxicity.⁵

REFERENCES

1. Testing cabozantinib in patients with advanced pancreatic neuroendocrine and carcinoid tumors. Updated March 25, 2025. Accessed March 26, 2025. https://clinicaltrials.gov/study/NCT03375320

2. Pancreatic neuroendocrine tumors. Mayo Clinic. April 30, 2024. Accessed March 26, 2025. https://www.mayoclinic.org/diseases-conditions/pancreatic-neuroendocrine-tumors/symptoms-causes/syc-20352489

3. Survival rates for pancreatic neuroendocrine tumor. American Cancer Society. March 1, 2023. Accessed March 26, 2025. https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/detection-diagnosis-staging/survival-rates.html

4. Cabozantinib extends survival in patients with RCC and untreated brain metastases. Pharmacy Times. February 15, 2025. Accessed March 26, 2025. https://www.pharmacytimes.com/view/cabozantinib-extends-survival-in-rcc-patients-with-untreated-brain-metastases

5. 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