title: Pharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma.
abstract: BACKGROUND
  Nivolumab is a recombinant, humanized monoclonal antibody that binds PD-1. The binding of PD-1 with PD-L1, expressed on antigen-presenting cells and tumor cells, suppresses the ability of T-lymphocytes to recognize and destroy tumor cells. Nivolumab reverts this inhibitory signal and has led to a significant prolongation of overall survival in patients with metastatic renal cell carcinoma (RCC).
  
  
  METHODS
  The rationale for immunotherapy in metastatic RCC, key immune checkpoint pathways, nivolumab pharmacodynamics, results from the main clinical trials, and predictors of response are discussed.
  
  
  CONCLUSIONS
  Nivolumab demonstrated a statistically significant advantage over everolimus in overall survival in metastatic RCC patients after first-line antiangiogenic therapy. Nevertheless, a number of issues remain to be resolved regarding the use of this drug in RCC. It is now imperative to identify which patients can benefit most from immunotherapy and studies are ongoing to define its role in other settings and/or in combinations with antiCTLA4 or antiangiogenic drugs.
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Farolfi
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Schepisi
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Conteduca
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Salvatore Luca
authors.initials: SL
authors.lastname: Burgio
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Lolli
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab
keywords: Anti-PD1 inhibitor; immune checkpoint inhibitor; metastatic renal cell carcinoma; nivolumab; predictive factors