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Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

A - Regimen Name

CABO Regimen
Cabozantinib
(Tablet)


Disease Site
Genitourinary
Renal Cell / Kidney


Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

For the treatment of adult patients with advanced or metastatic renal cell carcinoma (RCC) that had progressed after prior vascular endothelial growth factor (VEGF)-targeted therapy.


Supplementary Public Funding

cabozantinib (tablet)
Exceptional Access Program (cabozantinib - For the treatment of advanced renal cell carcinoma (RCC) according to clinical criteria) (EAP Website)

 
B - Drug Regimen

cabozantinib (tablet)
60 mg PO Daily

Cabozantinib tablets and capsules are not interchangeable.

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C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate – Consider prophylaxis daily

Other Supportive Care:

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. 

Prior to initiating cabozantinib therapy:

  • Blood pressure should be well-controlled.

  • Hypokalemia, hypomagnesemia, and hypocalcemia should be corrected.

  • Optimal control of thyroid function is recommended.

  • An oral examination is recommended.

     

Hold treatment for at least 28 days prior to scheduled surgery, including dental surgery; resume based on clinical judgment of adequate wound healing.

 

Dosage with toxicity

 Dose Levels

Dose Level Cabozantinib (Tablet) Dose (mg/day)
0 60
-1 40
-2* 20
-3 Discontinue

*If previously receiving lowest dose, restart at the same dose if tolerated. Otherwise, discontinue.

Toxicity Severity Action
Palmar-Plantar Erythrodysesthesia Intolerable Grade 2 or Grade 3 Hold**; restart at 1 dose level ↓
Hypertension

Intolerable Grade 2

OR

Grade 3
Hold**, restart at 1 dose level ↓

Grade 4 (including hypertensive crisis)

OR

Severe uncontrolled hypertension despite optimal therapy

Discontinue
Proteinuria Grade 2 or 3 Hold**, restart at 1 dose level ↓
Grade 4 (including nephrotic syndrome) Discontinue
Osteonecrosis of the jaw (ONJ) Any

Hold until complete resolution.

Restart at 1 dose level ↓

Unmanageable fistula or GI perforation Any Discontinue
Severe hemorrhage
Arterial or venous thromboembolic event that requires medical intervention (e.g., MI, cerebral infarction)
Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia
Posterior reversible leukoencephalopathy syndrome (PRES)
Wound healing complications requiring medical intervention
Other related hematologic/ non-hematologic/ organ toxicity Intolerable grade 2 and cannot be adequately managed Hold**; restart at 1 dose level ↓^
≥ Grade 3#

**Restart if toxicity resolved to ≤ grade 1 or baseline. Discontinue if toxicity does not resolve after 6 weeks.

#Including diarrhea that cannot be managed with standard antidiarrheal treatments.

^Or consider discontinuing for persistent or recurrent significant GI toxicity.



Hepatic Impairment

Liver Impairment Cabozantinib (Tablet) Starting Dose (mg/day)
Mild (Child-Pugh class A) No dosage adjustment required. Monitor patient closely.
Moderate (Child-Pugh class B) 40 mg. Monitor patient closely.
Severe (Child-Pugh class C) Not recommended (has not been studied)

Renal Impairment

 

Renal Impairment Cabozantinib (Tablet) Dose (mg/day)
Mild or moderate (eGFR ≥ 30mL/min) No dosage adjustment required
Severe (eGFR <29 mL/min) Not recommended (has not been studied)

Dosage in the Elderly

No dosage adjustment is required. There were no overall differences in safety or efficacy between patients aged 65 or older and younger patients.

 

 

 


 
F - Adverse Effects

Refer to cabozantinib (tablet) drug monograph(s) for additional details of adverse effects


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Diarrhea (may be severe)
  • Fatigue
  • Nausea, vomiting
  • Anorexia, weight loss
  • Hypertension (may be severe)
  • PPES
  • ↑ LFTs (may be severe)
  • Constipation
  • Dysgeusia
  • Rash, dry skin
  • Abdominal pain
  • Abnormal electrolytes (↓ PO4, Mg, Ca, Na, K)
  • Mucositis
  • Hypothyroidism
  • Dysphonia
  • Cough, dyspnea
  • Anemia
  • Musculoskeletal pain
  • Dyspepsia
  • Proteinuria
  • Thrombocytopenia
  • Dizziness
  • Headache
  • Arterial / venous thromboembolism
  • Artery aneurysm / dissection
  • QT/PR prolongation
  • Hemorrhage
  • Wound complications
  • GI fistula/ perforation
  • Cholestasis
  • Hepatotoxicity
  • Hepatic encephalopathy
  • Pancreatitis
  • Osteonecrosis of jaw
  • PRES
  • Seizure
  • Pleural effusion
 
G - Interactions

Refer to cabozantinib (tablet) drug monograph(s) for additional details


Cabozantinib is primarily metabolized by CYP3A4 and is susceptible to inhibitors and inducers of this isoenzyme.

  • Consider alternatives to strong CYP3A4 inhibitors. If concurrent use with a strong inhibitor cannot be avoided, reduce cabozantinib dose by 20 mg. 2 to 3 days after discontinuation of the strong inhibitor, resume cabozantinib at previous dose.

  • Avoid chronic co-administration with strong CYP3A4 inducers. If concurrent use cannot be avoided, increase cabozantinib dose by 20 mg as tolerated. 2 to 3 days after discontinuation of the strong inducers, resume cabozantinib at previous dose. Do not exceed a daily dose of 80 mg.

  • Avoid co-administration to the extent possible with drugs that decrease heart rate or prolong QT/PR interval as concurrent use may increase the risk of life-threatening arrhythmias and bradycardia.

 
H - Drug Administration and Special Precautions

Refer to cabozantinib (tablet) drug monograph(s) for additional details


Administration

  • Tablets should be administered on an empty stomach, at least 1 hour before or at least 2 hours after food.

  • Tablets should be swallowed whole, not chewed or crushed.

  • Avoid grapefruit, starfruit, Seville oranges, their juices or products during treatment.

  • If a dose is missed, an additional dose should not be taken within 12 hours of the next dose.

  • Cabozantinib should be stored between 15oC to 25oC

 

Contraindications

  • Patients who have a hypersensitivity to this drug or to any components of the formulation.

 

Other Warnings / Precautions:

  • Patients with a history of severe bleeding should be evaluated carefully before starting treatment. Do not give cabozantinib to patients with or at risk for severe hemorrhage or a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

  • Patients with cardiac impairment were excluded from clinical studies.

  • Use cabozantinib with caution in patients at risk for, or who have a history of:

    • Venous and/or arterial thromboembolism

    • Hypertension

    • Inflammatory bowel disease, tumour infiltration in the GI tract, or complications from prior GI surgery (particularly when associated with delayed or incomplete healing)

    • Severe bleeding

    • Low heart rate at baseline (< 60 beats per minute).

    • Syncope/arrhythmia, QT prolongation, sick sinus syndrome, sinoatrial block, atrioventricular (AV) block, ischemic heart disease, or congestive heart failure

    • Wound complications

  • Tablets contain lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

  • Use caution when driving or operating machinery as cabozantinib may cause fatigues, dizziness and weakness.

 

Pregnancy and Lactation:

  • Cabozantinib is not recommended for use in pregnancy. At least 2 forms of adequate contraception should be used by both sexes during treatment, and for at least 4 months after the last dose.

  • The effect of cabozantinib on oral contraceptives has not been studied; an additional contraceptive method (e.g. barrier) is recommended.

  • Breastfeeding is not recommended during treatment and for 4 months after the last dose.

  • Fertility effects: Probable. Documented in animals

 
I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

  • ECG, heart rate and blood pressure; Baseline and as clinically indicated

  • Electrolytes, including calcium, potassium and magnesium; Baseline and as clinically indicated, especially in patients at risk of severe arrhythmias

  • Liver function tests; Baseline and as clinically indicated

  • Renal function tests; Baseline and as clinically indicated

  • Thyroid function tests; Baseline and as clinically indicated

  • Clinical toxicity assessment for GI effects (including perforations, fistulas), bleeding, skin effects including PPES, respiratory and neurologic effects, thromboembolism, proteinuria, pancreatitis, osteonecrosis of the jaw and wound healing complications; At each visit

  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

     

Suggested Clinical Monitoring

  • INR for patients receiving warfarin; Baseline and as clinically indicated

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K - References

Cabozantinib Drug Monograph, Ontario Health (Cancer Care Ontario).

Choueiri TK, Escudier B, Powles T et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015;373:1814-23.

March 2022 Updated Premedication and Supportive Measures, Dose Modifications, Adverse Effects, Interactions, Drug Administration and Special Precautions, and Recommended Clinical Monitoring sections


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.