Pharmacokinetics, pharmacodynamics and clinical efficacy of nivolumab in the treatment of metastatic renal cell carcinoma

Expert Opin Drug Metab Toxicol. 2016 Sep;12(9):1089-96. doi: 10.1080/17425255.2016.1214713. Epub 2016 Jul 29.

Abstract

Introduction: 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).

Areas covered: 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.

Expert opinion: 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.

Keywords: Anti-PD1 inhibitor; immune checkpoint inhibitor; metastatic renal cell carcinoma; nivolumab; predictive factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / metabolism
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Humans
  • Immunotherapy / methods
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Neoplasm Metastasis
  • Nivolumab
  • Programmed Cell Death 1 Receptor / metabolism
  • Survival Rate
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab