Melanoma

Question 1

What is the pathogenesis of Melanomia?

Answer 1

• Melanocytes [located on skin, eye,…] help with protecting the tissues from UV radiation induced damage –> malignant transformation

Question 2

What are some of the risk factors for Melanomia?

Answer 2

• Genetics [FAMMS or HDNS]
• Sun [UV B light: SUNSCREEN protects]
• Internittent overexposure [skin is not use to it]

Question 3

What are some of the types of Melanoma that can form?

Answer 3

• Superficial Spreading
• Nodular
• Lentigo Maligna
• Acral Lentiginous
• Uveal

Question 4

What is Superficial Spreading Melanoma?

Answer 4

• Most common [70%]
• Flat, Irregular, Asymmetrical
• RAPID growth

Question 5

What is Nodular Melanoma?

Answer 5

• 15% - Aggressive
• Dark blue-black
• Located on Head, Neck, Trunk

Question 6

What is Lentigo Malinga Melanoma?

Answer 6

• On the face
• Brown

Question 7

What is Acral Lentiginous Melanoma?

Answer 7

• On palms, soles, under nails beds
• MORE common in African Americans, Asians, and Hispanics

Question 8

What is Uveal Melanoma?

Answer 8

• Within the eye
• Metastasis to liver

Question 9

What are the ABCDE’s of Melanoma?

Answer 9

• A: Asymmetric [not round]
• B: Borders
• C: Colors [black, blue, brown, yellow…]
• D: Diameter [Growth?]
• E: Evolution [change over time]

Question 10

If a skin lesion is suspected, what is the way to remove it?

Answer 10

• Digging it out
• Thin slices on exposed areas
• CHECK BRAF

Question 11

What is the way that we are able to surgically remove Melanoma?

Answer 11

• Dig out
• Mohs Surgery [thin slices]

Question 12

What is the treatment overview for Melanoma?

Answer 12

• Stage I or IIA [Early]: Clinical trail or observe
• Stage IIB or IIC [Early]: Clinical trail, Observe, Pembrolizumab]
• Stage III [Early]: Nivolumab, Pembrolizumab or Dabrafrnib/Trametinib

Question 13

In what way was Nivolumab chosen over Ipilimumab in Adjuvant therapy for Melanoma?

Answer 13

• Based on Checkmate 238 Trial
• Ipilimumab has more toxicities –> Use Nivolumab Alone

Question 14

In what way was Pembrolizumab chosen over Ipilimumab in Adjuvant therapy for Melanoma?

Answer 14

• Pembrolizumab approved for Stage III resected

Question 15

What is the use for Adjuvant Dabrafenib/Trametinib in Melanona?

Answer 15

• Completely resected, stage II disease with BRAF V600

Question 16

Why cant you use Dabrafinib alone in Melanoma?

Answer 16

• Dabrafinib can cause BRAF to activate in normal cells = skin cancer
• Trametinib inhibits MEK stopping this from happening

Question 17

What are some of the 1st line treatment options for Metastatic Melanoma?

Answer 17

• PD-1 inhibitors [Nivolumab or Pembrolizumab]
• BRAF + MEK [ONLY if BRAF Mutation]
• Nivolumab/Ipilimumab [maybe - high toxicities]

Question 18

What are some of the 2nd line treatment options for Metastatic Melanoma?

Answer 18

• Same as 1st line?
• Chemo [ONLY IF NEED BE - Paclitaxel]

Question 19

What do we start with first, when treating Melanoma?

Answer 19

• Immunotherapy should be started first then BRAF Mutation if there is a mutation [BRAF - is quick; Immunotherapy - takes weeks]

Question 20

What are the BRAF inhibitor that are used in Melanoma?

Answer 20

• VermuRAFenib, DaBRAFenib, EncoRAFenib

Question 21

What are the MEK inhibitors that are used in Melanoma?

Answer 21

• Trametinib, Cobimetinib, Binimetinib

Question 22

What is Vemurafenib?

Answer 22

• BRAF kinase Inhibitor taken WITH Cobmietinib
• QTc Prolongation
• Secondary Skin Cancers

Question 23

What is Cobmietinib?

Answer 23

• MEK inhibitor for unresectable or metastatic Melanoma
• Used with Vemurafenib

Question 24

What is Dabrafenib?

Answer 24

• BRAF Kinase Inhibitor taken WITH Trametinib
• Secondary Skin Cancers

Question 25

What is Trametinib?

Answer 25

- MEK Inhibitor that is selective for MEK 1 & 2 --> decreasing cell proliferation and increases apoptosis - Used with Dabrafenib

Question 26

What is Encorafenib?

Answer 26

- BRAF Kinase Inhibitor taken WITH Binimetinib [1st line?] - Causes less fever [fevers affect dosages]

Question 27

What is Binimetinib?

Answer 27

- MEK-1 Inhibitor that is used in combo with Encorafenib - Less fevers [Affects dosages]

Question 28

What is important to know about the BRAF inhibitors?

Answer 28

- Taken alone, resistance can develop in 6 months - why we take MEK inhibitor with it

Question 29

What is Ipilimumab?

Answer 29

- CTLA-4: down regulates the T-cell activation promoting antitumor immunity - Approved in unresectable and metastatic

Question 30

What are some of the toxicites that can show from taking Immunotherapy in Melanoma?

Answer 30

- Immune Mediated Colitis - Immune Mediated Diabetes - Immune Mediated Hypophysitis

Question 31

EXAMPLE: What would the regimen be for a patient that has Stage II melanoma?

Answer 31

- Pembrolizumab or Surgery or Observation for 1 YEAR

Question 32

EXAMPLE: What would the regimen be for a patient that has Stage III Melanoma?

Answer 32

- BRAF Mutation or NAH - NO: Pembrolizumab - YA: Pembrolizumab + Dabrafinib/Trametinib or Observation

Question 33

EXAMPLE: What would the regimen be for first line metastatic melanoma

Answer 33

- BRAF Mutation or NAH - NO: Pembrolizumab - YA: Pembrolizumab + BRAF/MEK