Malignant Melanoma

Question 1

What are the 3 main types of skin cancer?

Answer 1

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

Question 2

Where is the highest incidence of melanoma?

Answer 2

Australia and New Zealand

Question 3

What are the indicators of melanomas?

Answer 3

Asymmetry
Border
Colour
Diameter (>6mm)
Evolution or elevation
Funny mole

Question 4

What are the risk factors for melanoma?

Answer 4

Sun exposure
Number of moles
Skin type
Family history

Question 5

How are stage 0-3 tumours treated?

Answer 5

Excision of tumour followed by wide local excision to remove a good margin of healthy tissue

Question 6

What percentage of stage 3 tumours recur?

Answer 6

> 50%

Question 7

How is a stage 4 tumour treated?

Answer 7

Chemo
Biological therapies e.g. ipilimumab, nivolumab, pembrolizumab
TKIs e.g. vemurafenib, dabrafenib, trametinib

Question 8

what used to be the mainstay chemo treatment for stage 4 melanoma?

Answer 8

Dacarbazine

Question 9

What is dacarbazine?

Answer 9

Alkylating agent

Question 10

What was the first agent to show an increased overall survival in MM?

Answer 10

Ipilimumab

Question 11

What is ipilimumab?

Answer 11

Recombinant human monoclonal antibody that binds to CTLA-4. Blocks interaction of CTLA-4 with its ligands, CD80 and CD86

Question 12

What does CTLA-4 do?

Answer 12

Serves as an ‘immune checkpoint’ that down regulates pathways of T cell activation and prevents autoimmunity

Question 13

What does ipilimumab do by blocking the function of CLTA-4?

Answer 13

Potentiates the antitumour T-cell response, resulting in unrestrained T-cell proliferation

Question 14

What are the side effects of ipilimumab?

Answer 14

Diarrhoea
Rash
Pruritus
Fatigue
Nausea and vomiting
Decreased appetite
Abdominal pain
Colitis, hepatitis

Question 15

What is ipilimumab approved for?

Answer 15

Previously untreated advanced MM or after prior therapy

Question 16

What is the cost of one dose of ipilimumab?

Answer 16

£25,000 (given every 3 weeks for 4 doses total)

Question 17

What is Nivolumab?

Answer 17

Human immunoglobulin monoclonal antibody. anti-PD-1 (prgrammed death receptor-1)

Question 18

How does Nivolumab work?

Answer 18

Blocks the interaction between PD-1 found on T cells and its ligands PD-L1 and PD-L2

Question 19

What effect does blocking the interaction of PD-1 with its ligand have?

Answer 19

Nivolumab releases the PD-1 pathway mediated inhibition of the immune respone, oncluding the anti-tumour immune response

Question 20

What is Nivolumab licensed for?

Answer 20

To be given as dual therapy with ipilimumab in metastatic melanoma

Question 21

Why is dual therapy with Ipilimumab and Nivolumab restricted in practice to carefully selected patients?

Answer 21

Due to its risk of serious immune-mediated reactions-hepatitis, colitis

Question 22

What are the side effects of Nivolumab?

Answer 22

Fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia and diarrhoea.
Immune mediated adverse reactions e.g. penumonitis, colitis, hepatitis

Question 23

What is pembrolizumab?

Answer 23

PD-1 inhibitor

Question 24

Is Pembrolizumab given as monotheraoy or dual therapy?

Answer 24

Monotherapy

Question 25

What is pembrolizumab indicated for?

Answer 25

Previously untreated advanced MM or following ipilimumab/BRAF inhibitor

Question 26

What are the side effects of pembrolizumab?

Answer 26

Similar to Nivolumab side effects

Question 27

What is vemurafenib?

Answer 27

Oral tyrosine kinase inhibitor-BRAF inhibitor

Question 28

What happens when BRAF gene is mutated?

Answer 28

It becomes constitutively active which causes cell proliferation and tumour growth

Question 29

Who is vemurafenib only suitable for?

Answer 29

Patients with BRAF V600 mutation (glut-->valine)

Question 30

What are the side effects or vemurafenib?

Answer 30

``` Fatigue Joint pain Rash Sensitivity to sun Nausea Alopecia Pruritus Headahce Cutaneous squamous cell carcinomas ```

Question 31

How should vemurafenib be taken?

Answer 31

Preferably with food twice a day. Continue until disease progression/unacceptable toxicity

Question 32

What is vemurafenib NICE approved for?

Answer 32

Patients with advanced MM who have the BRAF V600 mutation

Question 33

What is dabrafenib?

Answer 33

Also a Raf inhibitor

Question 34

What are the side effects of Dabrafenib?

Answer 34

``` Fever Fatigue Joint pain Rash Headache Nausea Diarrhoea Cutaneous squamous cell carcinoma Uveitis ```

Question 35

How is dabrafenib taken?

Answer 35

Taken orally twice a day on empty stomach

Question 36

What is the prophylaxis for neutropenic patients?

Answer 36

Antibiotic 3.g ciprofloxacin broad spectrum cover good g-be cover Antifubhals e.g nystatin, fluconazole, itraconazole Mouthcare-chlorhexidine mw