Keytruda (Pembrolizumab): First PD-1 Inhibitor Approved for Previously Treated Unresectable or Metastatic Melanoma.

Melanoma, although not the most common skin cancer in the United States, is the most deadly.1 Based on data collected between 2004 and 2010, the 5-year survival rate for Americans with metastatic melanoma remains very low—only 16%—for all ages and races, and both sexes.2 The National Cancer Institute has estimated that 21.3 in 100,000 people will be diagnosed with melanoma of the skin in the United States in 2014.2 More than 9700 patients are estimated to die from melanoma in the same time frame.2 The incidence of melanoma is increasing in the United States, particularly among children and adolescents.2,3 An analysis of first-time melanoma diagnoses in patients aged 18 to 39 years between 1970 and 2009 showed that the incidence of melanoma increased 8-fold among young women and 4-fold among young men.3 A study analyzing data from 1973 to 2009 documented an average increase of 2% annually in melanoma in children aged between 0 and 19 years, particularly in girls and those aged between 15 and 19 years.4 These trends in melanoma diagnosis rates are concerning in light of their potential impact on healthcare resource consumption. An assessment of Medicare claims data from 1991 to 2005 demonstrated that patients with melanoma, particularly those with metastatic disease, utilize substantial healthcare resources.5 In this study, patients with metastatic melanoma consumed an average of more than $11,000 monthly in total healthcare costs, the majority of which was related to inpatient hospital services.5 Of note, this cost analysis was conducted before the new targeted therapies for metastatic melanoma became available. Because tumor cells can spread to distant lymph nodes and to other organs, metastatic melanoma can be difficult to cure.6 Surgery and radiation therapy can be considered for tumors on the skin or for tumors that are localized to the lymph nodes. Metastases in internal organs can be surgically removed, depending on their number and location.6 The development of novel agents has significantly altered the management of patients with advanced disease. Today's armamentarium of systemic treatments for metastatic melanoma includes immunotherapies, BRAF inhibitors (ie, vemurafenib, dabrafenib, trametinib), and chemotherapy.6 Many of these newer agents offer superior efficacy compared with chemotherapy.6 Specifically, immune checkpoint blockade with immuno-oncology agents that are directed toward cytotoxic T-lymphocyte antigen (CTLA)-4 (eg, ipilimumab), as well as programmed death (PD)-1 and PD-ligand 1 (PD-L1), has emerged as a successful treatment approach.7 Ipilimumab was the first CTLA-4 inhibitor to demonstrate an overall survival benefit and durable objective responses in patients with metastatic melanoma.7 In patients with metastatic melanoma and BRAF V600 mutation, a striking contrast has been observed between BRAF inhibition, which offers higher response rates with limited response durability, and CTLA-4 inhibition, which offers a relatively low response rate but very durable responses.7 To increase the number of patients with melanoma who benefit from durable responses with immunotherapy, researchers are exploring potential synergies between immune checkpoint inhibitors that target CTLA-4, PD-1, and PD-L1, and kinase-targeted therapies, as well as the concurrent and sequential use of CTLA-4 and PD-1/PD-L1 inhibitors.7