title: Evaluation of the pharmacokinetics and metabolism of pembrolizumab in the treatment of melanoma.
abstract: BACKGROUND
  Advanced melanoma is a devastating disease that has propelled research in therapeutics beyond chemotherapy and radiotherapy. Being highly immunogenic, melanoma is a model tumor for immunotherapy and has highlighted the therapeutic potential of the immune checkpoint inhibitors.
  
  
  METHODS
  This review discusses the pharmacologic properties, clinical efficacy, and safety profile of pembrolizumab, an IgG4-kappa humanized monoclonal antibody against the programmed cell death protein 1 (PD-1) receptor, for the treatment of unresectable or metastatic melanoma.
  
  
  CONCLUSIONS
  Pembrolizumab was the first PD-1 inhibitor to be approved by the U.S. Food and Drug Administration (FDA). Remarkably, this accelerated approval for the treatment of advanced, heavily pretreated melanoma was based on response rates alone from a phase I trial. As anticipated, pembrolizumab confirmed a survival advantage in phase II and III trials and has led the way for the study of other drugs that share its mechanism of action. Defining disease and patient characteristics associated with a response remains amongst the most pressing priorities.
authors.affiliation: a University of California , Irvine Medical Center , Orange , CA , USA.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Longoria
authors.affiliation: a University of California , Irvine Medical Center , Orange , CA , USA.
authors.forename: Krishnansu S
authors.initials: KS
authors.lastname: Tewari
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D017277:Drug Approval; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D014481:United States
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D061026:Programmed Cell Death 1 Receptor; C582435:pembrolizumab
keywords: Immune checkpoint; PD-1; melanoma; pembrolizumab