Joint Melanoma Simposium ESMO EORTC

Richard Marais
Where next with the next targeted therapies ?

Principles of advances
Combining laboratory with clinical research
Braf is mutated in 45 % in melanoma
Remarkable responses but relapses are coming
resistance mechanisms that are not completely  understood
PAN RAF inhibitors overcoming this resistence and are now in trials tested

Circulating tumour DNA to be evaluated -to measure what the tumour is doing and how the disease progressing , monitoring the disease.

Good study cases
To understand the disease and to send then the patient to the scan
then you look to the mutations

The case of a lady with mucosal melanoma
-DNA sequences in circulating DNA
- she had in two tumours kind -one with kit mutations responding to imatinib

Circulating Tumours DNA trials
Patient derived xenografts - close  relationship with pathologists
Problem is timing to take Braf inhibitors -is important for the time of progression
Rare Braf mutations + HRAS mutation

Study case
By DNA sequences in circulating DNA paclitaxel + trametinib = effective
They did not put the patient on it because of randomisation-
they decided to treat him with immunotherapy -patient died.

Study case
over 600 000 mutations - trametinib alone, crisotinib alone did not work
Trametinib+ crizotinib - discovered to be good in patient xenograft tumours
This combination -to be given to the patient when progress is arising

P. Ascierto
Immuno offers long survival

Clinical biomarker signature - orients the selection of patients

PD-L1 expression level to select treatment for the patients? Better not.

Consider an integrative approach
Gene expression and tumour burden at baseline- that means before patients start the treatment:
IFNy signature
Neoepitope signature and mutational load
Biochemical responses

Caroline Robert
Combinations and rationale for combinations

Braf inhibitors could induce T cells infiltrations in melanoma metastasis, facilitating further the action of immunotherapies