Monitoring monoclonal antibody delivery in oncology: the example of bevacizumab

• Published in: PloS one 2013-08, Vol.8 (8), p.e72021
• Main Authors: Nugue, Guillaume, Bidart, Marie, Arlotto, Marie, Mousseau, Mireille, Berger, François, Pelletier, Laurent
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Angiogenesis; Angiogenesis inhibitors; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Bevacizumab; Bioindicators; Biomarkers; Blood; Brain cancer; Brain Neoplasms - drug therapy; Breast cancer; Breast Neoplasms - drug therapy; Cancer; Cancer therapies; Chemotherapy; Colorectal cancer; Delivery scheduling; Drug dosages; FDA approval; Female; Glioma; Health aspects; Humans; Immunoglobulins; Immunotherapy; Life Sciences; Male; Medicine; Metastasis; Middle Aged; Monoclonal antibodies; Neoplasms - drug therapy; Neurosciences; Oncology; Patients; Pharmaceutical sciences; Sensitivity analysis; Side effects; Targeted cancer therapy; Therapy; Treatment Outcome; Tumors; Vascular endothelial growth factor; Vascularization
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0072021

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 (6(th)) 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.