Regretfully, a phase IV study including two cohorts (cohort 1: vemurafenib was administrated for 6 weeks prior to HD IL-2 treatment; cohort 2: vemurafenib was administrated for 7 to 18 weeks with stable or responding disease prior to starting HD IL-2) demonstrated that combination of HD IL-2 with vemurafenib did not show the synergy in treatment of BRAF-mutated metastatic melanoma except expected response with either agent alone (154). This evidence concerns the gene IL2 and metastatic melanoma.