Study Design
CABINET (Alliance A021602) was a multicenter, randomized, double-blind, placebo-controlled Phase III trial sponsored by the National Cancer Institute and conducted through the Alliance for Clinical Trials in Oncology
It enrolled a total of approximately 298 patients in the U.S., divided into two cohorts:
- Pancreatic NETs (pNET): ~95–99 patients
- Extrapancreatic NETs (epNET): ~199–203 patients
Patients were randomized in a 2:1 ratio (cabozantinib vs. placebo) and were stratified by factors like tumor site, grade, and prior therapies
Upon confirmed disease progression, patients were unblinded, and those on placebo could cross over to cabozantinib
Key Findings
Progression-Free Survival (PFS)
- pNET cohort:
- Median PFS with cabozantinib: 13.8 months
- Versus placebo: 4.4 months
- Hazard Ratio (HR): 0.23, p < 0.0001
- epNET cohort:
- Median PFS with cabozantinib: 8.4 months
- Versus placebo: 3.9 months
- HR: 0.38, p < 0.0001
These results were confirmed via blinded independent central review
Objective Response Rates (ORR)
- pNET: 19% response with cabozantinib vs. 0% with placebo
- epNET: 5% response with cabozantinib vs. 0% with placebo
Overall Survival (OS)
Interim OS analyses showed hazard ratios of 0.95 in the pNET cohort and 0.86 in the epNET cohort, indicating a trend toward survival benefit, though not yet statistically definitive
Safety Profile
Adverse events were consistent with known effects of cabozantinib and included hypertension, fatigue, and diarrhea. No new safety signals were identified
Regulatory Status & Impact
- The trial was stopped early and unblinded in August 2023 due to strong efficacy per an independent DSMB recommendation
- Final results were presented at ESMO 2024 and published in the New England Journal of Medicine
- Exelixis submitted a supplemental New Drug Application (sNDA) to the FDA, which was accepted in August 2024. The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025
- On March 26, 2025, the FDA approved cabozantinib for use in adults and pediatric patients aged 12+ with previously treated, unresectable or metastatic well‑differentiated pNET and epNET
Summary Table
| Cohort | Median PFS (Cabozantinib vs. Placebo) | Hazard Ratio | ORR (Cabozantinib) | OS Trend |
|---|---|---|---|---|
| pNET | 13.8 months vs. 4.4 months | 0.23 | 19% | HR 0.95 |
| epNET | 8.4 months vs. 3.9 months | 0.38 | 5% | HR 0.86 |
In summary, CABINET is a landmark Phase III trial showing that cabozantinib notably prolonged PFS in both pancreatic and extrapancreatic NETs, with a manageable safety profile and promising trends in overall survival. The drug has since received FDA approval, potentially offering a valuable new treatment option for patients with NETs that have progressed after prior therapies.