The most appropriate next step in management is BRAF V600 mutation analysis. Approximately 50% to 70% of cutaneous melanomas carry mutations in BRAF, a gene coding for a protein that leads to tumor activation though the mitogen-activated protein kinase (MAPK) pathway; 80% to 90% of these are the V600E mutation, with the remainder being other mutations at the V600 position. Inhibitors of BRAF are associated with response rates of over 50% and improved overall and progression-free survival in metastatic melanoma with a V600 mutation. Therefore, all patients with metastatic melanoma should have their tumor tested for the presence of driver V600 BRAF mutation to determine whether treatment with a BRAF inhibitor is a therapeutic option. Vemurafenib and dabrafenib are the available BRAF inhibitors. These agents have a rapid onset of action and are preferred over immunotherapy for initial treatment in patients with poor risk characteristics, including visceral metastases to sites other than the lung, an elevated serum lactate dehydrogenase, or a poor performance status. If a V600 mutation is present in this patient with liver metastases and an elevated serum lactate dehydrogenase, treatment with a BRAF inhibitor should be offered as a treatment option.

Chemotherapy with dacarbazine, the only chemotherapeutic agent approved for treatment of metastatic melanoma, has a response rate of only 7% to 12% and has not been shown to improve overall survival. It is usually reserved for patients who are not candidates for high-dose interleukin-2 (IL-2), ipilimumab, or BRAF inhibitor therapy.

High-dose interferon alfa is used as adjuvant therapy for patients with nonmetastatic melanoma who are at high risk for recurrence but is inferior to other immunotherapy options, including ipilimumab and high-dose IL-2, for patients with metastatic melanoma.

Ipilimumab is a monoclonal antibody that targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), which is a normal immune checkpoint molecule that down-regulates pathways of T-cell activation. CTLA-4 inhibition unleashes an immune response against the tumor. In patients with metastatic melanoma, treatment with ipilimumab improves overall survival. However, the response to ipilimumab can be delayed and there can be transient worsening of disease initially. In patients with poor prognostic features and a BRAF V600 mutation, the more rapid response of a BRAF inhibitor is preferred. If this patient's melanoma does not have a driver BRAF mutation, then treatment with ipilimumab would be offered.