Pharmacokinetics/Pharmacodynamic (PK/PD) relationship of therapeutic monoclonal antibodies used in oncology: what's new?

Eur J Cancer. 2020 Mar:128:103-106. doi: 10.1016/j.ejca.2020.01.004. Epub 2020 Feb 20.

Abstract

Monoclonal antibodies in oncology, used as targeted molecular therapy, linked to cytotoxic compound or directed against immune checkpoints, feature complex PKs essentially determined by their physicochemical characteristics. The increasing number of studies shows the existence of Pharmacokinetics/Pharmacodynamic (PK/PD) relationships for many of them. Although more studies, especially conducted in early clinical phases, are needed, existing studies highlight the need to integrate PK data for monoclonal antibodies in all phases of their development and the therapeutic management of patients with cancer. The current challenge is to identify non-responders as soon as possible. The use of monoclonal antibody dosage to determine the patient's PK profile and, as a result, the disease activity profile could therefore be an early predictive marker to help physicians optimise the strategy to be pursued, including dose adjustment, prolongation of the dose interval or even discontinuation of treatment.

Keywords: Antibody–drug conjugates; Cancer; Checkpoint inhibitors; Monoclonal antibodies; PD properties; PKs; Therapeutic drug monitoring.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents, Immunological / chemistry
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Chemistry, Pharmaceutical
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Humans
  • Models, Biological*
  • Molecular Structure
  • Molecular Targeted Therapy / methods*
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Time Factors
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological