Malignant melanoma

Question 1

What are the three main types of skin cancer?

Answer 1

Malignant melanoma

Non-melanoma skin cancers: basal cell carcinoma (BCC) and squamous cell carcinoma

Question 2

Who is primarily affected by melanoma?

Answer 2

White skinned people

Incidence is approx. equal in men and women

Question 3

Where are melanomas commonly found (in terms of location on the body)?

Answer 3

Faces and backs of white men and limbs of white women

Question 4

What does the acronym ABCD(EF) stand for in terms of identifying melanomas?

Answer 4

A - asymmetry, half of the mole does not match the other half
B - border (edges are irregular)
C - color, varies throughout
D - diameter, generally >6mm
E - evolution or elevation 
F- funny mole

Question 5

What are the risk factors for skin cancer?

Answer 5

Sun exposure - exposure to intermittent intense sun is more of a risk factor than prolonged exposure to UV radiation
Number of moles - the more moles there are, the more likely that one will become melanomous
Skin type - high risk if fair hair or fair skin
Family history

Question 6

How is melanoma diagnosed?

Answer 6

Examination using a dermascope
Excisional biopsy
Histopathology

Question 7

How is melanoma staged?

Answer 7

0 - melanoma in situ
1A - <1mm thick
1B - <1mm thick but skin broken/ulcerated
2A/B/C - larger and no spread to lymph nodes/other organs
3A - spread to up to 3 lymph nodes
3B/C - more lymph nodes/ulceration
4- metastatic

Question 8

How is stage 1-3 melanoma treated?

Answer 8

Excision of tumor followed by wide local excision of healthy tissue

Question 9

How is stage 4 melanoma treated?

Answer 9

Chemotherapy and biological therapies

Question 10

What is the chemotherapy regimen of choice for melanoma?

Answer 10

Dacarbazine

Question 11

What is Ipilimab? How does it work?

Answer 11

A recombinant human monoclonal antibody that binds to CTLA-4.

Blocks CTLA-4 interaction with its ligands CD80 and CD86

The CTLA-4 molecule serves as an immune checkpoint that downregulates the pathways of T cell activation and prevents autoimmunity –> thus the drug is thought to work through a T-cell mediated antitumor immune response.

Question 12

What is vemurafenib? Who is this treatment suitable for?

Answer 12

Oral tyrosine kinase inhibitor - BRAF inhibitor.
BRAF is mutated in 60% of melanomas and becomes constitutively active driving cell proliferation.
Only suitable for patients with BRAF V600 mutation,

Question 13

What is BRAF? What is its relation to melanoma?

Answer 13

tyrosine kinase. BRAF is mutated in 60% of melanomas and becomes constitutively active driving cell proliferation.

BRAF600 mutations - glutamate for guanine point mutation.

Question 14

What is dabrafenib?

Answer 14

BRAF inhibitor

Question 15

Why might dabrafenib be preferred over vemurafenib?

Answer 15

Similar efficacy but side effects tend to be tolerable

Question 16

What is pembrolizumab?

Answer 16

‘immuno-oncology’ therapy. Anti PD-1

PD-1 = programmed death receptor. Is found on T cells, blocks the interaction with its ligands PDL1 and PDL2, this stops inhibition of the immune response.

Question 17

What biological agent tends to the first line treated for stage 4 melanomas without the BRAF600 mutation?

Answer 17

Pembrolizumab - cheaper and more tolerable side effects.

Question 18

What is Trametinib?

Answer 18

A reversible high selective allosteric inhibitor of mitogen activated extracellular signal-regulated kinase 1 and 2 (MEK1/MEK2) activation.

In melanoma this pathway is often activated by mutated forms of BRAF which activates MEK. so used in patients with BRAF600 mutation.

Question 19

What is important monitoring required with trametinib?

Answer 19

Elevations in BP have been reported in association with trametinib as monotherapy and in combination with dabrafenib, in patients with or without pre-existing hypertension.

BP should be monitored at baseline and monitored during treatment with trametinib with control of hypertension by standard therapy as appropriate.