Pharmacokinetics and pharmacodynamics of approved monoclonal antibody therapy for colorectal cancer

Expert Opin Drug Metab Toxicol. 2022 Nov;18(11):755-767. doi: 10.1080/17425255.2022.2160316. Epub 2022 Dec 29.

Abstract

Introduction: The introduction of monoclonal antibodies to the chemotherapy backbone treatment has challenged the paradigm of metastatic colorectal cancer (mCRC) treatment. Their mechanism of action and pharmacokinetics are complex but important to understand in order to improve patient selection and treatment outcomes for mCRC population.

Areas covered: This review examines the scientific data, pharmacodynamics, and pharmacokinetics of approved monoclonal antibodies used to treat mCRC patients, including agents targeting signaling via VEGFR (bevacizumab and ramucirumab), EGFR (cetuximab and panitumumab), HER2/3 target therapy, and immunotherapy agents such as pembrolizumab or nivolumab. Efficacy and mechanism of action of bispecific antibodies are also covered.

Expert opinion: mCRC is a heterogeneous disease and the optimal selection and sequence of treatments is challenging. Monoclonal antibodies have complex pharmacokinetics and pharmacodynamics, with important interactions between them. The arrival of bioequivalent molecules to the market increases the need for the characterization of pharmacokinetics and pharmacodynamics of classic monoclonal antibodies to reach bioequivalent novel molecules.

Keywords: Bispecific antibody; colorectal cancer; monoclonal antibody; pharmacodynamics; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents* / pharmacology
  • Cetuximab / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • ErbB Receptors / therapeutic use
  • Humans
  • Immunotherapy

Substances

  • Antineoplastic Agents
  • ErbB Receptors
  • Antibodies, Monoclonal
  • Cetuximab