Melanoma

Question 1

What is CTLA-4

Answer 1

A regulatory protein. Sits on surface of T cells- when binds to B7, dampens activation of that T cell when being stimulated and costimulated by dendritic cells.

Ab against CTLA-4 is ipilimumab which turns off this dampening of the immune response

Question 2

What is PD-1

Answer 2

PD-1 is an immune protein on the surface of effector T cells. When it binds to PD-L1 on the cancer tissue cells, shuts down the T cell hence limiting autoreactivity against cancer cells. Anti PD1 antibody turns off this turning off effect in order to drive the immune response against the cancer.

Question 3

Side effects of ipilimumab

Answer 3

Rash
Diarrhoea
Autoimmune hepatitis
Autoimmune thyroiditis

Severity determines how should be managed

Immune related adverse events: seldom life threatening if recognised. eg hypopit,thyroid, adrenal - should not need to give anti-immune therapies eg steroids

Life threatening skin rash or hepatitis or colitis- give high dose steroids and may need immunosuppressive agents.

There are treatment algorithms

Question 4

name of anti-PD1

Answer 4

pembrolizumab
nivolumab

well tolerated
fewer immune side effects

CR rate 10% but overall clinical benfit (CR +PR + stabilistaion) is over 50%

Question 5

What is meant by an immune check point.

Answer 5

T cell activity is regulated by various immune check points in order to limit collateral tissue damage during the immune response

Question 6

What is dabrafenib and how does it work?

Answer 6

Melanoma new drug.
Targets MAP kinase pathway -BRAF inhibitor.
Oral agent.

Question 7

What is vemurafenib and how does it work?

Answer 7

Melanoma new drug.
Targets MAP kinase pathway -BRAF inhibitor.
Oral agent.

45 percent of melanomas have the BRAF mutation which makes the MAPK pathway constitutively active

This promotes proliferation and prevents apoptosis

Question 8

What is trametinib and how does it work?

Answer 8

MEK inhibitor of MAP kinase pathway

New melanoma drug

Question 9

What is cobimetinib and how does it work?

Answer 9

MEK inhibitor of MAP kinase pathway

New melanoma drug

Question 10

What are the side effects of vemurafenib?

Answer 10

rash
arthralgias
photosensitivity
LFTs
keratoacanthoma and SCCs

Question 11

What are the side effect so Trametinib?

Answer 11

rash
diarrhoea
peripheral oedema
asymptomatic reduction in LVEF
blurred vision, central retinal occlusion, detachment

Question 12

What are the side effects of dabrafenib?

Answer 12

DRUG FEVER
alopecia
skin
arthralgias
SCC, keratoacanthomas

Question 13

Is it better to use BRAF and MEK inhibitors together or separately?

Answer 13

Together

Question 14

Does it make a difference if PD-L1 expression or not

Answer 14

pembro yes increase response rate

nivol no

Question 15

Umbrella vs basket study

Answer 15

basket all same mutation different cancers

umbrella all same cancer but different mutations

Question 16

What types of UV?

Answer 16

UVA and UVB

Question 17

most significant predictors of biological behaviour

Answer 17

depth

presence or absence of ulceration

Question 18

acral lentiginous most common type in what people

Answer 18

asian

Question 19

stain in melanoma

Answer 19

melaninA andS100

Question 20

Stage4 and what things make A B or C

Answer 20

subcut or nodal mets A
lung and normal LDH B
not lung or high LDH C

Question 21

staging

Answer 21

1- tumour under 1mm and no ulceration or 1-2mm and no ulceration or under 1mm and ulceration
2-deeper but no LN
3-LN
4-mets

stage 1 non need for imaging to look at rest of body

Question 22

why take out LN in melanoma stage 3

Answer 22

no survival benefit

but palliative benefit as cause pain

Question 23

if brain mets, what can you do

Answer 23

resect if single lesion
stereotactic if three under 3cm
multiple mets- whole brain

survival advantage

Question 24

Who is BRAF mutated

Answer 24

tends to be those with intermittent sun exposure

KIT is if chronic sun exposure

if lots of acral exposure, tends to be NRAS and KIT

mucosal tends to be KIT

Question 25

dabraf vs vemuraf

Answer 25

Vem is V600E mutation specific, does NOT get into CNS

Dabraf is not V600E specific, gets into CNS

need to give both with trametinib

Question 26

APPROACH to metastatic melanoma

Answer 26

1. is it resectable
2. If not resectable what is the BRAF status? IF can, put on BRAF/MEK comb
3. If no BRAF mutation then put on Anti PD1 agent

Question 27

Fotemustine used when

Answer 27

rapidly advancing disease with cerebral mets