Cabometyx

Cabozantinib

• Brand(s): Cabometyx
• Dosage Form/Strength: 20 mg, 40 mg, 60 mg tablet
• Effective date: May 6, 2020 (mRCC)
  Updated: December 29, 2021 (HCC); February 8, 2024 (DTC); October 18, 2024 (mRCC)

Advanced Renal Cell Carcinoma

Initiation Criteria:

For the treatment of patients with advanced or metastatic renal cell carcinoma (RCC) meeting all of the following criteria prior to starting treatment with cabozantinib:

1. Patient is 18 years of age and older;
   AND
2. Diagnosed with advanced (i.e., not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma (RCC);
   AND
3. Patient will be using cabozantinib in one of the following clinical settings:
   i) As first line treatment in combination with nivolumab in patients with any risk category (i.e. good, intermediate or poor risk) (Note 1) who have not received prior systemic therapy for advanced or metastatic RCC (Note 2 and 3);
   OR
   ii) As second line monotherapy treatment in patients with any risk category (i.e., good, intermediate or poor risk) (Note 1) after progression on sunitinib or pazopanib used as first line. If used in this second line setting after monotherapy, only one of cabozantinib or axitinib or nivolumab will be funded.
   OR
   iii) As second line monotherapy treatment in patients with any risk category (i.e., good, intermediate or poor risk) (Note 1) after progression on a combination regimen of lenvatinib and pembrolizumab used as first line. In this setting, only one of cabozantinib or axitinib will be funded.
   OR
   iv) As second line monotherapy treatment in in patients with any risk category (i.e., good, intermediate or poor risk) (Note 1) after progression on a combination regimen of axitinib and pembrolizumab used as first line;
   OR
   v) As third line monotherapy treatment in patients with any risk category (i.e., good, intermediate or poor risk) (Note 1) after progression on sunitinib or pazopanib in first line AND nivolumab monotherapy in second line.
   OR
   vi) As third line monotherapy treatment in patients with intermediate or poor risk (Note 1) after progression on ipilimumab-nivolumab combination in first line and sunitinib or pazopanib in second line. If used in this third line setting, only one of cabozantinib or axitinib will be funded.

Exclusion Criteria:

• Patients who have experienced progression on cabozantinib for advanced or metastatic RCC will not be considered for EAP reimbursement for retreatment with cabozantinib in a subsequent line.
• Cabozantinib will not be funded for patients with advanced or metastatic RCC when used as fourth or later line therapy.*

*Case-by-case consideration may be provided for patients who have experienced disease progression or intolerance to everolimus or temsirolimus or sorafenib used for advanced or metastatic RCC.

Notes:

1. Patient’s risk stratification as per the International Metastatic RCC Database Consortium (IMDC), however, other equivalent risk stratifications will be considered on a case-by-case basis.
2. Patients who have used pembrolizumab in the adjuvant setting will only be eligible for funding of first line combination of cabozantinib and nivolumab for advanced or metastatic RCC if they have experienced a disease-free interval of 6 months or longer after completion of adjuvant therapy. It should be noted that patients will only be eligible for one line of an immune checkpoint inhibitor-based therapy for advanced or metastatic RCC.
3. Patients who experience unacceptable toxicity to either cabozantinib or nivolumab may continue treatment with the other agent until disease progression (up to a maximum of 2 years for nivolumab).

Renewal criteria:

Renewals for cabozantinib will be considered until clinically meaningful disease progression or the patient has experienced unacceptable toxicity.

Recommended dose:
- Requests for 20 mg should include reasons why the lower dosed tablets are required.
- Monotherapy: Cabozantinib 60 mg daily as monotherapy.
- Combination therapy: Cabozantinib 40 mg daily until disease progression with 240 mg of nivolumab intravenously every 2 weeks for a maximum period of 24 months

Approval duration (initials and renewals): 1 year

Advanced Hepatocellular Carcinoma

Initiation Criteria:

For the treatment of unresectable, advanced hepatocellular carcinoma (HCC) in adult patients meeting all of the following criteria prior to starting treatment with cabozantinib:

1. Patient is 18 years of age and older;
   AND
2. Cabozantinib will be used as monotherapy for HCC;
   AND
3. Cabozantinib will be used as second line therapy in a patient who has experienced disease progression during treatment with sorafenib OR lenvatinib for HCC;
   AND
4. Patient has good performance status with Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 1;
   AND
5. Has a Child-Pugh class A liver function.

Exclusion criteria: Patients meeting any of the following criteria will not be funded:

• Cabozantinib will not be funded in combination therapy with another therapy for HCC.
• Cabozantinib will not be funded in patients with Child-Pugh class status of B or C.
• Cabozantinib will not be funded as first-line therapy.

Notes

1. Only one of regorafenib or cabozantinib for the treatment of unresectable HCC will be funded in the second line setting.
2. Cabozantinib can be funded in patients who develop intolerances or toxicities to regorafenib and wish to switch to cabozantinib as long as they have not experienced disease progression on regorafenib and meet the initial funding criteria for cabozantinib.

Recommended dose: 60 mg orally once daily

Requests for 20 mg and 40 mg tablets should include reasons why the lower dosed tablets are required.

Renewal criteria:

Renewals will be considered until clinically meaningful disease progression¹ or the patient has experienced unacceptable toxicity.

Please provide radiographic and/or scan results indicating no progression.

¹Evaluation according to Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria.

Duration of Approval for Initials and Renewals: 3 months

Cabozantinib for differentiated thyroid cancer

Initiation Criteria:

For the treatment of adult patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC) who meet the following criteria:

1. Patient is 18 years of age or older;
   AND
2. Has locally advanced or metastatic differentiated thyroid carcinoma that is histologically or cytologically confirmed;
   AND
3. Patient’s DTC is refractory or resistant to radioactive iodine (RAI) (Note 1);
   AND
4.  Patient has been previously treated with at least one other vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitor (TKI) (Note 2);
   AND
5. Patient will be using cabozantinib meeting one of the following circumstances:
   i) Patient is using cabozantinib as third line treatment after experiencing failure of, or resistance to first-line treatment with RAI (Note 1) and second line-treatment with lenvatinib or sorafenib (Note 2);
   OR
   ii) Patient is using cabozantinib as fourth line after experiencing failure or resistance to first line treatment with RAI (Note 1), then second line-treatment with lenvatinib or sorafenib (Note 2), and third-line treatment with selpercatinib;
   AND
6. Patient has good performance status;
   AND
7. Cabozantinib is not being used in combination with other anticancer therapies for DTC;
   AND
8. Prescribed by an authorized prescriber with expertise in the management of thyroid cancer.

Renewal criteria:

Renewal of funding will be considered in patients who are not experiencing disease progression (Note 3) or unacceptable toxicity to cabozantinib.

Notes:

1. Patients with an intolerance, contraindication or deemed ineligible for the use of radioactive iodine therapy can be considered for funding on a case-by-case basis. Please provide details of the intolerance or contraindication with your request.
2. Although sorafenib is not funded for the treatment of DTC under the Ontario drug benefit program, patients who have used sorafenib for DTC rather than lenvatinib can be considered.
3. Response should be measured using clinical assessment, biochemical markers, and radiological imaging.

Recommended dose: Up to 60 mg once daily.

Requests for 20 mg and 40 mg tablets should include reasons why the lower dosed tablets are required.

Approval duration of initials and renewals: 1 year

EAP Drug Request Form:

Standard Form for EAP Drug Requests