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Introduction

Melanoma is the most deadly form of skin cancer and one of the most resistant of all cancers to modern chemotherapy.¹ The global incidence of disease has increased to about 132 000 per year, driven primarily by new cases in Western nations.² Experts attribute the growth to increasing recreational exposure to ultraviolet radiation and heightened emphasis on early detection. Melanoma risk factors include skin, hair color, and the pre-existence of more than 20 benign nevi. For these reasons, Caucasian patients are 5 and 10 times more likely than Asian and black patients, respectively, to develop the disease.³ Each year, more than 10 000 people in the United States die from melanoma.⁴

Patients who present with a thin (<1 mm) primary melanoma will have a cure rate of more than 95%, while the 5-year survival rate of those with regional lymph-node involvement can be as high 70%.⁵ However, about 20% of melanoma patients have metastases to distant organs at the time of diagnosis; historically, these individuals have been considered incurable: the overall 5-year survival rate for this cohort remains less than 10%. According to the American Joint Committee on Cancer Melanoma Staging (AJCCMS), the best prognosis is for metastases to be in the skin, subcutaneous tissue, or lymph nodes.⁷ Patients with lung metastases, or a combination of lung and skin or subcutaneous metastases, have an intermediate prognosis. The poorest prognosis is for patients with metastases to other sites (the liver, bone, and brain) or any site combined with an elevated lactate dehydrogenase. The AJCCMS database estimates the 1-year survival rates for these 3 prognostic groups to be 62%, 53%, and 33%, respectively.⁶

Recent discoveries in immunology have led to the introduction of drugs called checkpoint inhibitors, which turn off normal brakes in the immune system. These drugs, which comprise a single anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and 2 anti-programmed death-1 (PD-1) antibodies, have revolutionized the treatment of patients with metastatic melanoma. The therapies have dramatically improved outcomes and have significantly increased the rates of response, progression-free survival (PFS), and overall survival (OS). This new generation of pharmacotherapies will be the focus of this educational activity.