This site is intended for US healthcare professionals only

For the first time, a Phase 3 trial encompasses the wide-ranging heterogeneity of NET1-6

On This Page:

CABINET: A randomized (2:1), double-blind, placebo-controlled, NCI-sponsored Phase 3 trial1,6 

 

Patients with neuroendocrine tumors (NET) (N=298)1

Pancreatic NET
(pNET) (N=99)
Stratified by concurrent SSA and prior sunitinib use

Extrapancreatic NET
(epNET) (N=199)
Stratified by concurrent SSA use and primary site

RANDOMIZED 2:1

RANDOMIZED 2:1

CABOMETYX® (cabozantinib)
60 mg once daily (± SSA)
(n=66)

Placebo
Once daily (± SSA)
(n=33)
 

CABOMETYX
60 mg once daily (± SSA)
(n=132)

Placebo
Once daily (± SSA)
(n=67)

Disease progression

Disease progression

Disease progression

Disease progression

 

CROSSOVER*

 

CROSSOVER*

 

Open-label
CABOMETYX
60 mg daily (± SSA)

 

Open-label
CABOMETYX
60 mg daily (± SSA)

  • Primary endpoint: PFS by BIRC1 
  • Secondary endpoints: ORR, OS, safety, and tolerability6†
*

Unblinding and crossover to open-label CABOMETYX allowed after confirmation of progressive disease by real-time central radiology review.1

†

As recommended by the Data and Safety Monitoring Board, the CABINET trial was unblinded before the final prespecified efficacy analysis, allowing all remaining placebo patients to cross over to CABOMETYX.1

 

Inclusion criteria6:
  • Progression or intolerance following ≥1 FDA-approved systemic therapy, not including SSAs
  • Well- to moderately-differentiated NET
  • Functional and nonfunctional NET
  • Tumor Grades 1-3
  • ECOG PS 0-2
  • Disease progression ≤12 months before randomization
  • Concurrent SSA use permitted if a stable dose was received for ≥2 months
CABINET allowed all sites of origin, including the lungs, GI tract, and pancreas6 

CABINET was sponsored by the National Cancer Institute (NCI), a part of the National Institutes of Health, and initiated in 2018 by the NCI-funded National Clinical Trials Network group, the Alliance for Clinical Trials in Oncology (Alliance), to address the unmet needs in NET.6 

Tumor assessments were done every 12 weeks by radiographic imaging for tumor response and progression (as determined by RECIST v1.1).6

CABINET enrolled a broad patient population, allowing patients across all sites of origin6

CABINET patients by site of origin7

Percentages for the epNET cohort exceed 100 due to rounding.

‡Other sites included small bowel, mesentery, ampulla, midgut, hindgut, biliary tract, larynx, presacral space, kidney, and ethmoid sinus.7

CABINET evaluated a range of patients, >70% with Grade 2-3 tumors6,7

Tumor grade
  • Placebo arm tumor grade distribution for pNET: 21% Grade 1; 67% Grade 2; 9.1% Grade 3; 3% unknown
  • Placebo arm tumor grade distribution for epNET: 22% Grade 1; 67% Grade 2; 7.5% Grade 3; 3% unknown

Tumor grade percentages do not total 100 due to rounding.

Lu-177 dotatate use

Patients who received prior Lu-177 dotatate

SSA use

Patients who received concurrent SSA

Prior SSA use

Patients who received prior SSA

Hormone syndrome 

Patients with functional disease

Some patients had unknown functional status.  

CABINET was the first Phase 3 trial across pNET and epNET to include patients with prior peptide receptor radionuclide therapy (PRRT)3,5,8-10

Select patient demographics7

 

pNET cohort (N=99) 

epNET cohort (N=199) 

CABOMETYX
(n=66)

Placebo
(n=33)

CABOMETYX
(n=132)

Placebo
(n=67)

Median age in years (range) 

60 (29-78)

64 (39-79) 

66 (28-86)

66 (30-82)

Gender, n (%) 

    

Male/Female 

37 (56)/29 (44) 

19 (58)/14 (42)  

60 (45)/72 (55)  

37 (55)/30 (45) 

ECOG PS, n (%)  

    

0/1/2

36 (55)/
29 (44)/1 (1.5) 

18 (55)/
15 (45)/0  

48 (36)/
83 (63)/1 (0.8) 

29 (43)/
37 (55)/1 (1.5)  

Sites of metastatic disease, n (%) 

    

Liver

65 (98) 

30 (91) 

117 (89) 

62 (93)

Lymph nodes

30 (45) 

18 (55) 

91 (69) 

49 (73)

Bone

19 (29) 

7 (21) 

67 (51) 

33 (49) 

Lungs

4 (6)

2 (6)

29 (22) 

13 (19) 

Abdominal wall

3 (4.5) 

1 (3) 

10 (8) 

7 (10) 

Subcutaneous tissue

NA

NA

5 (3.8)

1 (1.5)

CNS/Brain

NA 

NA

4 (3) 

3 (4.5)

Other§ 

10 (15) 

5 (15) 

47 (36) 

23 (33)

Some percentages for each category exceed 100 due to rounding.  

§

For pNET, other sites included peritoneum, ovary, and spleen; for epNET, other sites included mesentery, peritoneum, omentum, ovary, pancreas, breast, and adrenal gland.7

See pNET Efficacy Data
See epNET Efficacy Data
Back to Top

BIRC=blinded independent review committee; CNS=central nervous system; ECOG PS=Eastern Cooperative Oncology Group performance status; GI=gastrointestinal; Lu-177=lutetium-177 NA=not available; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors; SSA=somatostatin analogue. 
 

References:

  1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc.
  2. AFINITOR® (everolimus) Prescribing Information. Novartis Pharmaceuticals Corporation.
  3. SUTENT® (sunitinib malate) Prescribing Information. Pfizer, Inc.
  4. LUTATHERA® (lutetium Lu-177 dotatate) Prescribing Information. Novartis Pharmaceuticals Corporation.
  5. SOMATULINE® DEPOT (lanreotide) Prescribing Information. Ipsen Pharma Biotech.
  6. Chan JA, Geyer S, Zemla T, et al. Phase 3 trial of cabozantinib in previously treated advanced neuroendocrine tumors. N Engl J Med. 2024; Published online September 16, 2024. doi:10.1056/NEJMoa2403991.
  7. Data on file. Exelixis, Inc.
  8. US Food and Drug Administration. FDA approves new treatment for certain digestive tract cancers. January 26, 2018. Accessed September 5, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-certain-digestive-tract-cancers.
  9. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514-523.
  10. Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968-977.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong or Moderate CYP3A4 Inducers: If coadministration with strong or moderate CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

Please see full Prescribing Information.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

Indication

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET).

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET)​.

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET).

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET)​.

visual type treatment for Exelixis logo

© 2025 Exelixis, Inc.  03/25 CA-3422