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PHRM 864: Therapeutics IV > Melanoma > Flashcards

Melanoma Flashcards

1
Q

What is the pathogenesis of Melanomia?

A
  • Melanocytes [located on skin, eye,…] help with protecting the tissues from UV radiation induced damage –> malignant transformation
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2
Q

What are some of the risk factors for Melanomia?

A
  • Genetics [FAMMS or HDNS]
  • Sun [UV B light: SUNSCREEN protects]
  • Internittent overexposure [skin is not use to it]
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3
Q

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

A
  • Superficial Spreading
  • Nodular
  • Lentigo Maligna
  • Acral Lentiginous
  • Uveal
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4
Q

What is Superficial Spreading Melanoma?

A
  • Most common [70%]
  • Flat, Irregular, Asymmetrical
  • RAPID growth
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5
Q

What is Nodular Melanoma?

A
  • 15% - Aggressive
  • Dark blue-black
  • Located on Head, Neck, Trunk
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6
Q

What is Lentigo Malinga Melanoma?

A
  • On the face
  • Brown
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7
Q

What is Acral Lentiginous Melanoma?

A
  • On palms, soles, under nails beds
  • MORE common in African Americans, Asians, and Hispanics
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8
Q

What is Uveal Melanoma?

A
  • Within the eye
  • Metastasis to liver
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9
Q

What are the ABCDE’s of Melanoma?

A
  • A: Asymmetric [not round]
  • B: Borders
  • C: Colors [black, blue, brown, yellow…]
  • D: Diameter [Growth?]
  • E: Evolution [change over time]
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10
Q

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

A
  • Digging it out
  • Thin slices on exposed areas
  • CHECK BRAF
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11
Q

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

A
  • Dig out
  • Mohs Surgery [thin slices]
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12
Q

What is the treatment overview for Melanoma?

A
  • 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
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13
Q

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

A
  • Based on Checkmate 238 Trial
  • Ipilimumab has more toxicities –> Use Nivolumab Alone
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14
Q

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

A
  • Pembrolizumab approved for Stage III resected
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15
Q

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

A
  • Completely resected, stage II disease with BRAF V600
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16
Q

Why cant you use Dabrafinib alone in Melanoma?

A
  • Dabrafinib can cause BRAF to activate in normal cells = skin cancer
  • Trametinib inhibits MEK stopping this from happening
17
Q

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

A
  • PD-1 inhibitors [Nivolumab or Pembrolizumab]
  • BRAF + MEK [ONLY if BRAF Mutation]
  • Nivolumab/Ipilimumab [maybe - high toxicities]
18
Q

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

A
  • Same as 1st line?
  • Chemo [ONLY IF NEED BE - Paclitaxel]
19
Q

What do we start with first, when treating Melanoma?

A
  • Immunotherapy should be started first then BRAF Mutation if there is a mutation [BRAF - is quick; Immunotherapy - takes weeks]
20
Q

What are the BRAF inhibitor that are used in Melanoma?

A
  • VermuRAFenib, DaBRAFenib, EncoRAFenib
21
Q

What are the MEK inhibitors that are used in Melanoma?

A
  • Trametinib, Cobimetinib, Binimetinib
22
Q

What is Vemurafenib?

A
  • BRAF kinase Inhibitor taken WITH Cobmietinib
  • QTc Prolongation
  • Secondary Skin Cancers
23
Q

What is Cobmietinib?

A
  • MEK inhibitor for unresectable or metastatic Melanoma
  • Used with Vemurafenib
24
Q

What is Dabrafenib?

A
  • BRAF Kinase Inhibitor taken WITH Trametinib
  • Secondary Skin Cancers
25
Q

What is Trametinib?

A
  • MEK Inhibitor that is selective for MEK 1 & 2 –> decreasing cell proliferation and increases apoptosis
  • Used with Dabrafenib
26
Q

What is Encorafenib?

A
  • BRAF Kinase Inhibitor taken WITH Binimetinib [1st line?]
  • Causes less fever [fevers affect dosages]
27
Q

What is Binimetinib?

A
  • MEK-1 Inhibitor that is used in combo with Encorafenib
  • Less fevers [Affects dosages]
28
Q

What is important to know about the BRAF inhibitors?

A
  • Taken alone, resistance can develop in 6 months - why we take MEK inhibitor with it
29
Q

What is Ipilimumab?

A
  • CTLA-4: down regulates the T-cell activation promoting antitumor immunity
  • Approved in unresectable and metastatic
30
Q

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

A
  • Immune Mediated Colitis
  • Immune Mediated Diabetes
  • Immune Mediated Hypophysitis
31
Q

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

A
  • Pembrolizumab or Surgery or Observation for 1 YEAR
32
Q

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

A
  • BRAF Mutation or NAH
  • NO: Pembrolizumab
  • YA: Pembrolizumab + Dabrafinib/Trametinib or Observation
33
Q

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

A
  • BRAF Mutation or NAH
  • NO: Pembrolizumab
  • YA: Pembrolizumab + BRAF/MEK

PHRM 864: Therapeutics IV (28 decks)

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