Braftovi

Encorafenib

• Brand(s): Braftovi
• Dosage Form/Strength: 75 mg capsule
• Effective date: December 6, 2022

For the treatment of patients with previously treated metastatic colorectal cancer (mCRC) with a BRAF V600E mutation as combination therapy with cetuximab in patients meeting ALL the following criteria:

1. Documented BRAF V600E-mutated mCRC detected by a validated test; AND

2. Has received at least 1 previous systemic treatment for mCRC but the previous treatment received was not with an epidermal growth factor receptor (EGFR) inhibitor or a BRAF inhibitor; AND

3. Patients must have good performance status (Eastern Cooperative Oncology Group (ECOG) equal to or less than 2); AND

4. Patients must have adequate organ function; AND

5. Encorafenib must be used in combination with cetuximab; AND

6. Prescribed by a clinician with expertise in the diagnosis and treatment of colorectal cancer.

Notes:

1. Combination therapy of encorafenib and panitumumab may be considered as an option to combination with cetuximab.

2. Patients should be assessed clinically every 2 to 4 weeks, with radiological assessments performed every 8 to 12 weeks.

3. In the event that encorafenib or cetuximab is discontinued due to unacceptable toxicity, the other drug must also be discontinued.

4. For a time-limited period, patients who are using cetuximab or panitumumab for mCRC who have not experienced disease progression on their current regimen and otherwise meet the above initiation criteria, may change their treatment regimen to add encorafenib to be used as dual combination therapy with cetuximab or panitumumab.

Exclusion Criteria:

• Patients with other types of BRAF mutations or whose BRAF status cannot be determined will not be funded.
• Encorafenib will not be funded as first line treatment for mCRC.
• Encorafenib will not be funded as monotherapy.

Renewal Criteria:
Combination dual therapy may be continued until evidence of disease progression based on RECIST criteria as determined by radiographic scans or development of unacceptable toxicity due to encorafenib or cetuximab (or panitumumab as applicable).

Approved dose: 300 mg orally once daily.

Approval duration: 1 year

Initiation Criteria:

For the mutation-targeted treatment of BRAF V600 mutation-positive locally advanced, unresectable melanoma or metastatic melanoma in patients who meet ALL the following criteria:

1. Encorafenib will be used in combination with binimetinib; AND

2. Has histologically confirmed BRAF V600 mutation positive locally advanced unresectable or metastatic cutaneous melanoma or unknown primary melanoma (stage IIIB, IIIC, or IV per AJCC); AND

3. Has not received a previous treatment (i.e. treatment naïve) for locally advanced or metastatic disease OR has progressed on a prior first line immunotherapy for locally advanced or metastatic disease; AND

4. Good performance status; AND

5. Has adequate organ, bone marrow and cardiac function; AND

6. Prescribed by a clinician with expertise in the diagnosis and management of melanoma.

Notes:

1. Encorafenib and binimetinib may be considered in patients who have previously received a BRAF inhibitor (BRAFi)/MEK inhibitor (MEKi) in the adjuvant setting if disease relapse occurs more than 6 months after completion of adjuvant BRAFi/MEKi treatment.

2. The Ministry will fund only one BRAF mutation targeted treatment/treatment regimen for locally advanced or metastatic melanoma.

3. If brain metastases are present, they should be treated or asymptomatic and stable.

4. For a time-limited period, requests in patients who have initiated another BRAFi or MEKi treatment regimen will be considered for a switch to encorafenib/bimetinib on a case-by-case basis upon having met the above initiation criteria at the time of BRAFi/MEKi initiation and ONLY IF there has been no disease progression.

5. Patients should be assessed for a response (as per RECIST 1.1) to treatment with encorafenib and binimetinib every 2 to 3 months.

6. Treatment should be discontinued in those who develop adverse reactions that do not resolve despite dose delays or dose reductions.

Exclusion Criteria:

• Uveal or mucosal melanoma are not funded.
• BRAF V600 negative, or wild type tumors, or unknown status will not be funded
• Patients who have experienced disease progression on a BRAF targeted regimen for locally advanced or metastatic melanoma.

Renewal requests:
Renewal of encorafenib in combination with binimetinib may be continued until evidence of disease progression or development of unacceptable toxicity requiring discontinuation.
A letter from the prescriber confirming no clinical or radiological disease progression by RECIST 1.1 should be included.

Recommended dose:
Encorafenib 450 mg once daily in combination with Binimetinib 45 mg twice daily

Approval duration (both initial and renewal requests): 6 months (patients should have their disease status assessed at least every 6 months)

EAP Drug Request Form:

Standard Form for EAP Drug Requests