Melanoma Flashcards
What percentage of all cancers dx in 2019 was melanoma?
11%
What are risk factors for melanoma?
Unprotected sun exposure Fair skin, light eye colour, light hair, tendaency to burn Dysplastic naevi Immunosuppresion Family history
Which genes are related to family hx of melanoma?
CDKN2A
CDK4
What are prognostic factors?
Tumour thickness Mitotic rate Ulceration Primary tumour location Old age and male sex Lymph node
What is the mx of stage 0?
Surgical resection
What is the mx of stage 1?
Surgical resection + consider sentinel LN bx
When is adjuvant RTx considered?
Stage II and III
Which mutation is the most important? Which is the prevalence?
BRAF
40%
What are other mutations are tested for?
NRAS
C-KIT
Which drugs inhibitor BRAF?
Vemurafenib and dabrafenib
What is the problem with BRAF inhibitors?
Development of resistance
Through which mechanism does resistance to BRAF inhibitors occur?
Via the MAPK reactivation through MEK
What do you combine BRAF inhibitors with?
MEK inhibitor
What is the name of MEK inhibitors?
Trametinib + cobimetinib
How do cancers evade the immune system?
Loss of antigenicity
Gain of immunosuppressive properties
Creating an immunosuppressive environment
What is the target of ipilimumab? What is the result?
CTLA4
Propagates T-cell activation
What are the PD-1 inhibitors?
Pembrolizumab
Nivolumab
What is the roll of PD-1 in the immune response?
Its activation causes downregulation of T cell response
What is the response rate with PD-1 inhibitors? What is hte median overall survival?
~50%
32-37 months
Is there benefit of combining ipilimumab and nivolumab
Yes - Response rate 61 vs 11% (CTLA4 alone)
What is the toxicity rate with combination immunotherapy?
44% grade 3 + 4 AE
What are the most common effected organs from immunotoxicity?
Skin GIT Liver Endo (thyroid, adrenals, pituitary) Lung
When is the peak onset of immunotoxicity?
4-12months
What is most common site of AE with ipilimumab and nivolumab respectivity?
GIT
Endocrine
How do you manage mild/moderate/severe immunotoxicity?
Mild - symptomatic mx
Moderate - PO pred 1mg/kg daily. Omit next dose until symptoms resolve
Severe - IV corticosteroids with wean over 4 weeks once severe resolve. Consider alt. immunosuppressive if not responding within 5-7 days. Consider ceasing agent.
What is the most common endocrinopathy?
Thyroiditis
What is pseudoprogression?
Phenomenon of apparent progression that then regresses
