Interim FDG PET-CT in Melanoma Metastatic Patient's Treated by Anti-PD1 Therapy

The management and prognosis of patients with metastatic cutaneous melanoma have changed dramatically with the advent of immunotherapy, especially anti-PD-1 antibodies. These immune-checkpoint inhibitor block the programmend cell death receptor 1 (PD1). Currently, two anti-PD-1 antibodies, nivolumab and pembrolizumab are available. Recent data for pembrolizumab show that the overall survival rate at almost 3 years is 50% and the overall response rate is 42%. Despite these results so far never achieved, about 60% of patients do not respond to anti-PD-1 immunotherapy and, at present, no clinical, imaging or biological markers are predictive of the therapeutic response. The identification of such markers is essential in order to guide the clinician in the choice of optimal treatment. The objective of this study is to assess whether FDG (18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose) PET-CT could be an early predictive method of therapeutic response to anti-PD-1 immunotherapy in metastatic melanoma. The anti-tumor immune response to anti-PD-1 is related to the activation of immune cells infiltrating the tumor, in particular CD8+ (cluster of differentiation 8) T cells whose phenotype is that of "exhausted T cells". This immune activation is such that it sometimes causes (about 10% of cases) a transient increase in the size and/or number of lesions. This phenomenon, has been called "pseudo-progression" and it cannot be interpreted routinely by RECIST1.1 criteria. The exact kinetics and timing of CD8+ T cell activation leading to response to treatment is still unknown. It is possible that this cellular activation has an early metabolic translation detectable by 18FDG PET-CT. The investigator's hypothesis is that early 18FDG PET-CT, ie after 2 cycles of anti-PD1 in metastatic patient melanoma, could be predictive of the therapeutic response. 20 patients will be enrolled and undergo three PET/CT scans: a baseline PET-CT (PET0) before the start of anti-PD1 treatment, an early PET-CT after 2 cycles of anti-PD1 (PET1) and a third PET-CT after 3 months of initiation of treatment. Treatment response on FDG PET will be assessed according to PERCIST criteria. Changes in FDG uptake will be correlated with blood results.