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Dosing for CABOMETYX® (cabozantinib) DTC monotherapy

In patients who are RAI-R or ineligible and progressed on a prior VEGFR-targeted therapy1

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CABOMETYX is available in three tablet strengths1

 

RECOMMENDED
STARTING DOSE*

FIRST
REDUCTION

SECOND
REDUCTION

Adult; pediatric†
≥40 kg

60 mg
daily

40 mg
daily

20 mg
daily‡

Pediatric†
<40 kg

40 mg
daily

20 mg
daily

20 mg
every
other day‡

 

Adult; pediatric†
≥40 kg

Pediatric†
<40 kg

RECOMMENDED STARTING DOSE*

60 mg daily

40 mg daily

FIRST REDUCTION

40 mg daily

20 mg daily

SECOND REDUCTION

20 mg daily‡

20 mg every other day‡

Tablets shown are not actual size.

*

Until disease progression or unacceptable toxicity, administer as recommended

†

Pediatric defined as patients 12 years of age and older.

‡

If previously receiving lowest dose, resume at same dose. If lowest dose not tolerated, discontinue CABOMETYX.

How to take CABOMETYX1

Administer on an empty stomach

Administer CABOMETYX at least 1 hour before or at least 2 hours after eating

Swallow CABOMETYX tablet whole

Do not crush, chew, or split CABOMETYX tablets

  • Withhold CABOMETYX for at least 3 weeks prior to elective surgery, including dental surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed, to reduce the risk of hemorrhage
  • Do not substitute CABOMETYX tablets with cabozantinib capsules
  • Do not administer CABOMETYX with food
  • Do not take a missed dose within 12 hours of the next dose
  • Modify the dose for certain patients with hepatic impairment and for patients taking drugs known to moderately or strongly induce or strongly inhibit CYP3A4

You can modify CABOMETYX dosing for safety and tolerability1

For intolerable Grade 2 ARs, Grade 3-4 ARs, and ONJ

Withhold CABOMETYX

Wait until improvement or resolution (return to baseline or resolution to Grade 1)

Restart CABOMETYX at a dose reduced by 20 mg
If previously receiving the lowest dose, resume at same dose. If lowest dose not tolerated, discontinue CABOMETYX1

Permanently discontinue CABOMETYX for Grade 3 or 4 hemorrhage, development of a GI perforation or Grade 4 fistula, acute myocardial infarction or Grade 2 or higher cerebral infarction, Grade 3 or 4 arterial thromboembolic events or Grade 4 venous thromboembolic events, Grade 4 hypertension/hypertensive crisis or Grade 3 hypertension/hypertensive crisis that cannot be controlled, nephrotic syndrome, or reversible posterior leukoencephalopathy syndrome.1

 

Pharmacokinetics

The predicted terminal half-life of CABOMETYX is approximately 99 hours.1

During the COSMIC-311 trial, the median average daily dose was 42.0 mg2

The overall efficacy results of CABOMETYX in the COSMIC-311 trial were achieved in the context of dose modifications1,3

5% in a circle represents the discontinuation rates from COSMIC-311 trial

CABOMETYX 
discontinuation rates 
due to ARs§
(Placebo 0%)

72% in a circle represents the number of doses withheld in COSMIC-311 trial

CABOMETYX
dose withholds
(Placebo 27%)

56% in a circle represents the number of dose reductions in COSMIC-311 trial

CABOMETYX 
dose reductions
(Placebo 5%)

4.3
weeks

CABOMETYX median time to dose interruption
(4.1 weeks with placebo)4

8.1
weeks

CABOMETYX median time to first dose reduction (40 mg) 
(12.1 weeks with placebo)4

16.1
weeks

CABOMETYX median time to second dose reduction (20 mg)
(n/a with placebo)4

The most frequent adverse reactions (≥5%) leading to dose reduction of CABOMETYX were PPE, diarrhea, fatigue, proteinuria, and decreased appetite. Dose interruptions occurred in 72% patients receiving CABOMETYX. Adverse reactions requiring dosage interruption in ≥5% of patients were PPE, diarrhea, dyspnea, hypertension, decreased appetite and proteinuria.1

§ARs leading to discontinuation included fatigue (n=2), arthralgia (n=1), diarrhea (n=1), hypercalcemia (n=1), hypertension (n=1), large-intestine perforation (n=1), increased liver function test (n=1), myalgia (n=1), and renal impairment (n=1); one patient could have more than one treatment-related AR.2

For eligible patients who have been prescribed CABOMETYX: Dose Exchange Program

Provides a free 15-tablet supply in the lower dose to help patients who require a dose reduction||¶

||

Additional restrictions and eligibility rules apply.  

Patients are required to return any unused product.

Learn More

This description of the Exelixis Access Services® (EASE) program is for informational purposes only. Exelixis® makes no representation or guarantee concerning reimbursement or coverage for any service or item. Information provided through the Exelixis Access Services program does not constitute medical or legal advice and is not intended to be a substitute for a consultation with a licensed health care provider, legal counsel, or applicable third-party payer(s). Exelixis reserves the right to modify the program at any time without notice.

Download the CABOMETYX Dosing and Administration Guide

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Download the CABOMETYX Treatment Management Guide

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AR=adverse reaction; CYP3A4=cytochrome P450 family 3 subfamily A member 4; DTC=differentiated thyroid cancer; GI=gastrointestinal; ONJ=osteonecrosis of the jaw; PPE=palmar-plantar erythrodysesthesia; RAI-R=radioactive iodine-refractory; VEGFR=vascular endothelial growth factor receptor.

References:

  1. CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc.
  2. Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22(8):1126-1138. doi.org/10.106/S1470-2045(21)00332-6
  3. Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial [supplementary appendix]. Lancet Oncol. 2021;22(8):1126-1138. doi. org/10.1016/ S1470-2045(21)00332-6
  4. European Medicines Agency: Committee for Medicinal Products for Human Use (CHMP). Assessment report: CABOMETYX. September 2018. Accessed September 15, 2022.

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.

Indications

CABOMETYX® (cabozantinib) 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, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

CABOMETYX® (cabozantinib) 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, in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with advanced renal cell carcinoma (RCC). 

CABOMETYX is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 

CABOMETYX is indicated for the treatment of adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.

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