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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†
BSA ≥ 1.2 m2		 60 mg
daily		 40 mg
daily		 20 mg
daily
Pediatric†
BSA < 1.2 m2		 40 mg
daily		 20 mg
daily    		 20 mg
every
other day
  Adult; pediatric†
BSA ≥ 1.2 m2		 Pediatric†
BSA < 1.2 m2
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 administered as recommended.

†

Pediatric defined as patients 12 years of age and older.

How to take CABOMETYX1

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

Swallow whole
DO NOT CRUSH TABLET

  • 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
  • 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 strongly induce or inhibit CYP3A4

You can modify CABOMETYX dosing for safety and tolerability.1

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 CABOMETYX.1

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; BSA=body surface area; CYP3A4=cytochrome P450 family 3 subfamily A member 4; 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, 2022.
  2. Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomized, 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. Assessed September 15, 2022.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as recommended. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

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. 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 with medical management; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients. Grade 3 diarrhea occurred in 10% of CABOMETYX 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): PPE occurred in 45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

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): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. 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, if possible. Withhold CABOMETYX for development of ONJ until complete resolution, resume at a reduced dose. 

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX 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): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: Thyroid dysfunction, primarily hypothyroidism, has been observed with CABOMETYX. Based on the safety population, thyroid dysfunction occurred in 19% of patients treated with CABOMETYX, including Grade 3 in 0.4% of patients.

Patients should be assessed for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitored for signs and symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid function testing and management of dysfunction should be performed as clinically indicated.

Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on the safety population, hypocalcemia occurred in 13% of patients treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1% of patients. Laboratory abnormality data were not collected in CABOSUN.

In COSMIC-311, hypocalcemia occurred in 36% of patients treated with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of patients.

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

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment 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, constipation. 

DRUG INTERACTIONS

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

Strong CYP3A4 Inducers: If coadministration with strong 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.

Please see accompanying 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 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 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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