Monitoring Monoclonal Antibody Delivery in Oncology: The Example of Bevacizumab

Abstract

Developing therapeutic monoclonal antibodies paves the way for new strategies in oncology using targeted therapy which should improve specificity. However, due to a lack of biomarkers, a personalized therapy scheme cannot always be applied with monoclonal antibodies. As a consequence, the efficacy or side effects associated with this type of treatment often appear to be sporadic. Bevacizumab is a therapeutic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF). It is used to limit tumor vascularization. No prognosis or response biomarker is associated with this antibody, we therefore assessed whether the administration protocol could be a possible cause of heterogeneous responses (or variable efficacy). To do this, we developed a bevacizumab assay with a broad sensitivity range to measure blood bevacizumab concentrations. We then analyzed bevacizumab concentrations in 17 patients throughout the first quarter of treatment. In line with previously published data, average blood concentrations were 88+/−27 mg/L following the first dose administered, and 213+/−105 mg/L after the last (6th) dose administered. However, the individual values were scattered, with a mean 4-fold difference between the lowest and the highest concentration for each dose administered. We demonstrated that the bevacizumab administration schedule results in a high inter-individual variability in terms of blood concentrations. Comparison of assay data with clinical data indicates that blood concentrations above the median are associated with side effects, whereas values below the median favor inefficacy. In conclusion, bevacizumab-based therapy could benefit from a personalized administration schedule including follow-up and adjustment of circulating bevacizumab concentrations.

Correlation Between Bevacizumab Exposure and Survival in Patients with Metastatic Colorectal Cancer

“…It has been previously reported that lower trough bevacizumab concentrations are associated with poorer clinical outcomes . However, our study for the first time has identified three distinct groups of subpopulations within patients with mCRC, where bevacizumab exposure is directly and positively related to OS.…”

Circulating Tumor Cells and Bevacizumab Pharmacokinetics during Neoadjuvant Treatment Combining Chemotherapy and Bevacizumab for Early Breast Cancer: Ancillary Analysis of the AVASTEM Trial

“…This is consistent with the known half-life (~19 days) and previously published PK data [ 28 ]. Average blood concentration of bevacizumab has indeed been described to be 88 mg/L after the first dose [ 29 ]. These data are very close to ours (median of 111 mg/L after one or two cycles) suggesting the robustness of our results.…”

Pharmacogenomics, Pharmacokinetics and Circulating Proteins As Biomarkers for Bevacizumab Treatment Optimization in Patients with Cancer: A Review

“…Low serum bevacizumab concentrations were associated with a lack of efficacy, while high concentrations were associated with side effects. Thus, they concluded that serum bevacizumab concentration appears to be a useful clinical pharmacodynamic marker [ 74 ]. In 2016 two other groups published their results regarding the role of bevacizumab plasma concentrations.…”