Assessment of exposure-response relationship for bevacizumab in patients with metastatic colorectal cancer

Biomed Pharmacother. 2021 Sep:141:111827. doi: 10.1016/j.biopha.2021.111827. Epub 2021 Jun 18.

Abstract

Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI: 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI: 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.

Keywords: Bevacizumab; Colorectal neoplasms; Drug monitoring; Exposure-response relationship; Treatment outcome.

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents, Immunological / pharmacokinetics
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Bevacizumab / pharmacokinetics
  • Bevacizumab / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / secondary*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Proportional Hazards Models
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Immunological
  • Bevacizumab