Treatment of Melanoma

Typically, Stage I, Stage II, and Stage III melanoma are treated by surgery. In Stage III melanoma, surgery may be followed by immunotherapy or targeted therapy. Stage III melanoma that is unresectable (or that cannot be treated with surgery), and Stage IV or advanced/metastatic melanoma are treated in the same manner with immunotherapy, targeted therapy, and rarely, chemotherapy. Additionally, palliative, or supportive therapies that address symptoms may also be prescribed, and these can include surgery to remove lymph nodes or radiation to treat tumors that have spread to a distant organ. Sometimes, surgery may be used in advanced melanoma if the cancer is limited to a few sites. Your team will consider many factors before deciding on your course of treatment including your age and overall health, the location and number of tumors, the speed at which the cancer is spreading, the presence of certain mutations in the tumor (eg, BRAF mutation), your personal preferences, and how to maintain your quality of life.¹

Your treatment armamentarium may include:²

• Oncolytic virus therapy including talimogene laherparepvec that is injected directly into your tumor
• Immunotherapy including ipilimumab, pembrolizumab, nivolumab, and interleukin-2 that are given as monotherapy or in combination as in the case of ipilimumab and nivolumab
• Targeted therapy including dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib, and binimetinib that are given as monotherapy or in combination therapy
• Chemotherapy
• Palliative therapy including surgery to remove lymph nodes or tumors in the brain, bone, GI tract, or lung, and radiation therapy to the brain, bone, or spinal cord
• Enrolling in a clinical trial

Immunotherapy uses the patient’s own immune system to fight the cancer. For advanced melanoma these can include the use of immune checkpoint inhibitors that block a protein (checkpoint) made by the patient’s own immune cells and some cancer cells. Checkpoint proteins act like brakes on your body’s immune responses and can sometimes keep immune cells from killing cancer cells. Blocking them allows your immune cells to kill the cancer cells. Currently there are three types of checkpoint inhibitors in use: CTLA-4 inhibitor ipilimumab, PD-1/PD-L1 inhibitors pembrolizumab, nivolumab and atezolizumab, and LAG-3 inhibitor relatlimab. Interleukin-2 helps to boost the activity of many of the patient’s own immune cells, especially lymphocytes which can then attack and kill cancer cells.²

Targeted therapy does exactly what the name says, it identifies and attacks specific cancer cells. Targeted therapy causes less damage to healthy cells than traditional chemotherapy or radiation therapy. Current targeted therapies include BRAF inhibitors that block the activity of proteins made by the BRAF genes that have undergone mutations (eg, dabrafenib, vemurafenib, encorafenib), and MEK inhibitors that block proteins called MEK1 and MEK2 that affect the survival of cancer cells (eg, trametinib, cobimetinib, binimetinib). Combinations of BRAF and MEK inhibitors can also be used to treat melanoma and some examples include dabrafenib plus trametinib, vemurafenib plus cobimetinib, and encorafenib plus binimetinib.¹