BRAF Inhibitors

Question 1

What drugs are in the BRAF Inhibitors class?

Answer 1

Drugs in this class are:
- Dabrafenib
- Vemurafenib
- Encorafenib

Question 2

What is the brand name of Dabrafenib?

Answer 2

The brand name of this generic drug is:
- Tafinlar

Question 3

What is the brand name of Vemurafenib?

Answer 3

The brand name of this generic drug is:
- Zelboraf

Question 4

What is the brand name of Encorafenib?

Answer 4

The brand name of this generic drug is:
- Braftovi

Question 5

What is the generic of name of Tafinlar?

Answer 5

The generic name of this brand name drug is:
- Dabrafenib

Question 6

What is the generic of name of Zelboraf?

Answer 6

The generic name of this brand name drug is:
- Vemurafenib

Question 7

What is the generic of name of Braftovi?

Answer 7

The generic name of this brand name drug is:
- Encorafenib

Question 8

What are the main indications for use of Dabrafenib?

Answer 8

The main indications of this drug are:
- Melanoma (with BRAFV6ooE or BRAFV6ooK mutation)
- Non-small cell lung cancer (with BRAF V6ooE mutation)
- Thyroid cancer (with BRAF V6ooE mutation)

Question 9

What are the main indications for use of Vemurafenib?

Answer 9

The main indications of this drug are:
- Melanoma (with BRAFV6ooE or BRAFV6ooK mutation)
- Non-small cell lung cancer (with BRAF V6ooE mutation)
- Erdheim-Chester disease (with BRAF V6oo mutation)

Question 10

What are the main indications for use of Encorafenib?

Answer 10

The main indications of this drug are:
- Melanoma (with BRAFV6ooE or BRAFV6ooK mutation)
- Colorectal cancer (with BRAF V6ooE mutation)

Question 11

What is the class and MOA of Dabrafenib?

Answer 11

This drug in the following class:
- BRAF Inhibitors

This drug’s MOA is as follows:
- Selectively targets mutated forms BRAF kinase (V600-) and interferes with the mitogen-activated protein kinase (MAPK) signaling pathway that regulates the proliferation and survival of melanoma cells.

Question 12

What is the class and MOA of Vemurafenib?

Answer 12

This drug in the following class:
- BRAF Inhibitors

This drug’s MOA is as follows:
- Selectively targets mutated forms BRAF kinase (V600-) and interferes with the mitogen-activated protein kinase (MAPK) signaling pathway that regulates the proliferation and survival of melanoma cells.

Question 13

What is the class and MOA of Encorafenib?

Answer 13

This drug in the following class:
- BRAF Inhibitors

This drug’s MOA is as follows:
- Selectively targets mutated forms BRAF kinase (V600-) and interferes with the mitogen-activated protein kinase (MAPK) signaling pathway that regulates the proliferation and survival of melanoma cells.

Question 14

What are the notable monitoring parameters for Vemurafenib?

Answer 14

The notable monitoring parameters for this drug are:
- See common parameters for class
- EKG at baseline. 15 days after initiation. then monthly for 3 months. then every 3 months thereafter (more frequently if clinically appropriate) and with dosage adjustments.

Question 15

What are the notable/common monitoring parameters for the BRAF Inhibitors class?

Answer 15

The notable/common monitoring parameters for this drug class are:
- BRAFV6ooK or V6ooE mutation status prior to treatment
- Dermatologic evaluations prior to initiation, every 2 months during therapy, and for up to 6 months following discontinuation to assess for new cutaneous malignancies

Question 16

What is the emetic potential of Dabrafenib?

Answer 16

The emetic potential of this drug is:
- Moderate - High

Question 17

What is the emetic potential of Vemurafenib?

Answer 17

The emetic potential of this drug is:
- Minimal - Low

Question 18

What is the emetic potential of Encorafenib?

Answer 18

The emetic potential of this drug is:
- Moderate - High

Question 19

Describe the emetic potential of the BRAF Inhibitors class.

Answer 19

The emetic potential of this drug class is:
- All moderate-high except for Vemurafenib (minimal-low)

Question 20

What drugs in the BRAF Inhibitors class have a moderate-high emetic potential?

Answer 20

Drugs in the class with a moderate-high emetic potential are:
- Dabrafenib
- Encorafenib

Question 21

What drugs in the BRAF Inhibitors class have a minimal-low emetic potential?

Answer 21

Drugs in the class with a minimal-low emetic potential are:
- Vemurafenib

Question 22

Describe the administration of Dabrafenib.

Answer 22

The administration of this drug is described as follows:
- Oral: Absorption decreased with a high fat meal (-1,000 calories: 58 to 75 grams of fat)

Question 23

Describe the administration of Vemurafenib.

Answer 23

The administration of this drug is described as follows:
- Oral

Question 24

Describe the administration of Encorafenib.

Answer 24

The administration of this drug is described as follows:
- Oral

Question 25

Describe the metabolism of Dabrafenib.

Answer 25

The metabolism of this drug is as follows:
- Patients with moderate (bilirubin >1,5 to 3 times ULN and any AST) or severe (bilirubin >3 to 10 times ULN and any AST) hepatic impairment may have increased exposure to this drug

Question 26

What are the notable ADRs of Vemurafenib?

Answer 26

The notable ADRs of this drug are:
- Secondary skin cancers
- QT prolongation

Question 27

What are the notable/common ADRs of the BRAF Inhibitors class?

Answer 27

The notable/common ADRs of this drug class are:
- Secondary skin cancers
- QT prolongation with Vemurafenib

Question 28

Describe the strategy and rationale for management of secondary skin cancers caused by BRAF inhibitors.

Answer 28

The strategy and rationale for management of this condition caused by this drug class are:
- Secondary cutaneous squamous cell cancers and keratoacanthomas are the result of compensatory RAF signaling seen with BRAF inhibition.
- The risk of these additional cancers is decreased with the addition of a MEK inhibitor.
- These cancers are typically localized and easily treated with surgical excision or topical fluorouracil cream.
- Regular skin assessments should be done throughout therapy with BRAF inhibitors.

Question 29

Describe the half-life of Encorafenib.

Answer 29

The half-life of this drug is described as follows:
- This drug has a longer dissociation half-life than other BRAF inhibitors, allowing for sustained inhibition of BRAF (and thus tumor growth)

Question 30

What are the clinical pearls of the BRAF Inhibitors class?

Answer 30

The clinical pearls of this drug class are as follows:
- Though the BRAF inhibitors were initially evaluated as single agents, combination therapy with a MEK inhibitor (ex: Trametinib) is now the recommended treatment regimen.

Question 31

Describe the therapy selection process for BRAF Inhibitors?

Answer 31

The therapy selection process for this drug class is as follows:
- All metastatic tumors should be evaluated for the V6oo mutation.
- In V6ooE or V6ooK mutated tumors, the initial selection between BRAF inhibitors and immunotherapy is commonly done based on the aggressive nature of the tumor.
- Rapidly growing tumors that are symptomatic are treated with BRAF-directed therapy because it generates a higher rate of response that occurs quicker, while asymptomatic or more indolent tumors may be treated with immunotherapy.

Question 32

Describe resistance among BRAF Inhibitors?

Answer 32

Resistance to this drug class is as follows:
- Though the BRAF inhibitors were initially evaluated as single agents, combination therapy with a MEK inhibitor (example: Trametinib) is now the recommended treatment regimen.
- This is due to the development of resistance to the single agent BRAF inhibitors after 6-7 months
- Combination therapy with both BRAF and MEK inhibitors may suppress the downstream resistance mechanism

Question 33

Describe the symptoms of melanoma.

Answer 33

Symptoms of this condition are:
- ABCDE: asymmetry, border, color, diameter, and evolving
- A: Asymmetry - melanomas are often asymmetrical
- B: Border - melanomas often have an irregular border
- C: Color - melanomas often have more than one color or shade in the mole
- D: Diameter: melanomas are often larger than 6mm, or the size of a pencil eraser
- E: Evolving: melanomas tend to change over time while benign moles do not