Vicki L4 - MM Flashcards
What are the 3 main types of skin cancers?
1) Malignant melanoma
2) Basal cell carcinoma (BCC)
3) Squamous cell carcinoma (SCC)
Identifying melanomas:
A,B,C,D,E,F
Asymmetry, border, colour, diameter (larger than 6mm), evolution, funny mole
Risk factors: (4)
1) Pale skin and hair
2) Previous exposure to sun/UV rays (especially if history of blistering sunburn) - exposure to intermittent sun in high doses worse than prolonged exposure, high incidence in Australia and new Zealand due to decreased ozone layer so more exposure to UV rays, sunbed usage
3) Increased number of moles
4) Family history if history in primary relative then 50% more likely to develop skin cancer
Treatment of melanoma:
Stage 0/1/2/3 = ____ of tumour followed by wide local ____ to remove good margin of healthy tissue.
Over 50% stage 3 tumours can become ___ _
Stage 4 = advanced/______ - spread to organs
______
______ ______ e.g. I____, P_____, V____, D_____
Excision
Excision
Stage 4
Unresectable
Chemotherapy
Biological therapy e.g ipilimumab, pembrolizumab, vemurafenib, dabrafenib
Advanced/_____ melanoma (stage 4)
10yr survival = __%
Da____ chemotherapy used to be mainstay (_____ agent)
Combination chemo regimen didn’t improve survival just ____.
Da____ has a 20% response rate and median duration of response is 5-6 months before disease progression and has no significant effect on __.
Unresectable 10% Dacarbazine (alkylating agent) Toxicity Dacarbazine OS (overall survival)
Ipilimumap:
Increased overall survival in ____/_____ MM.
- Median __ 10 months vs around 6 months with experimental glycoprotein injection (criticised study as not std treatment but shown that vaccine had little/no activity in MM)
- It is a _____ _____ ab
- Binds ___-_ to prevent it acting with ____ and ____ ligands
- ____-_ serves as an immune checkpoint that down regulates pathways of _ ___ activation and prevents autoimmunity SO if this is blocked by Ipilimumab then the anti tumour _ ___ response is potentiated. This leads to unrestricted _ ___ proliferation so the immune system can attack cancerous cells. Thus the MOA of Ipilimumabs effects in patients with melanoma is indirect, possibly through _ ___ mediated anti tumour immune responses.
Advanced/unresectable OS (overall survival) Humanised monoclonal antibody CTLA-4 to prevent it interacting with CD80 and CD86 CTLA-4 T cell T cell T cell T cell
More than __% of patients in trials with ipilimumab reported side effects due to increased/excessive immune activity. (9)
Fatigue Rash Pruritis Nausea and vomiting Diarrhoea Decreased appetite Abdominal pain Colitis Hepatitis
Ipilimumab is NICE approved for advanced (metastatic or unresectable) malignant melanoma that is previously ______ or for disease that has previously been ____. BUT it is VERY _____ and the manufacture needs to provide the drug at a _____ patient access ____.
Untreated
Treated
Expensive
Discounted patient access price
Vemurafenib:
- Is an oral ____ ____ ____ (____ inhibitor)
- The ____ gene is mutated in around 60% melanomas and become __________ active so cell proliferation and tumour growth occurs.
- It is only suitable for patients with the ___ ____ mutation (____ = position in ___ AA sequence is a substitution of glutamate for valine)
- 90% patients have tumour regression quickly
- 50-60% partial/complete response (won’t see on CT scan)
- Median __ = 15months
Tyrosine kinase inhibitor BRAF BRAF Constitutively BRAF V600 V600 BRAF OS (overall survival)
Vemurafenib side effects:
- Fatigue
- Rash (emollient, antihistamine, painkillers)
- Pruritis
- Nausea
- Alopecia
- Headache
- Joint pain (painkillers/heat or ice pack)
AND what is the other thing?
Cutaneous squamous cell carcinomas reported in 20% patients
- Minor skin cancers (less severe just cut out)
- Patients should be aware to check for any new/changing skin lesions
- Surgical removal
ALSO severe skin reactions reported rarely and pt should be told to stop treatment immediately if develop blistering of skin
How to take Vemurafenib:
- Tablets to be taken _____ ____ bd
- Continue until disease progression/unacceptable _____
- Metabolised by _____ enzymes so _____ _____
- Approved by NICE in patients with advanced MM who have ___ ____ mutation
With food bd
toxicity
CYP450 - drug interactions
BRAF V600
Dabrafenib
- Another _____ inhibitor with similar efficacy to ______
- NICE approved in those with advanced MM who have ____ ___ mutation.
- Tablets to be taken on an ____ ____ bd
- Metabolised by _____ enzymes so _____ _____.
Side effects include: fever (report if over 38), joint pain, headache, fatigue, rash, nausea and diarrhoea and also TWO others! What are they?
BRAF Vemurafenib BRAF V600 Empty stomach CYP450 enzymes so drug interactions
Cutaneous squamous cell carcinomas in 10% patients
RARE but also uveitis (inflammation of the eye) - can damage vision if not treated. Report is redness/irritation, blurred vision, eye pain, floating spots before the eye
Pembrolizumab
- Immuno-oncology therapy called anti __-_s (_____ ____ ____ _)
- Humanised _____ _____ given by IV infusion that blocks interaction between __-_ found on -___ and its ligands __-__ and __-.
- By blocking the ligand interaction with receptors, Prembrolizumab released __-_ pathway mediated inhibition of the _____ response including anti-tumour _____ response (i.e. takes the brakes off the immune system)
- PD-1s (programmed death receptor 1)
- Humanised monoclonal antibody given by IV infusion
- PD-1 found on T-cells and it’s ligands PD-L1 and PD-L2
- PD-1
- Immune
- Immune
Pembrolizumab estimated OS at 18 months - 62%
Overall response rate = around 25%
Indicated for ______ ____ advanced MM or following ipilimumab/____ inhibitor.
Side effects:
Fatigue, cough, nausea, pruritus and rash, decreased appetite, constipation, arthralgia and diarrhoea
AND _____ _____ adverse reactions e.g. _____, _____ and _____.
These are new drugs so a phone call from a nurse is conducted a few days after given the drug to see if side effects especially for ____ e.g. cough and SOB and also follow up calls are conducted.
Previously untreated
BRAF
Immune released
Pneumonitis, colitis, hepatitis
Pneumonitis
Summary of treatments for advanced/unresectable MM:
No BRAF ____ mutation
1st line: Either _____ or _____ (cheaper)
2nd line: the same but try the other one
BRAF ____ mutation
1st line: ______ or ______
2nd line: ______/_______
V600
Ipilimumab or Pembrolizumab
V600
Dabrafenib or vemurafenib
Ipilimumab/pembrolizumab
