Population pharmacokinetic meta-analysis of ramucirumab in cancer patients.

Abstract

AIMS:

Ramucirumab is a human IgG1 monoclonal antibody that specifically binds vascular endothelial growth factor receptor-2 (VEGFR-2) and blocks binding of VEGF-A, VEGF-C and VEGF-D. The objective of the analysis was to characterize the clinical pharmacology profile of ramucirumab using a population pharmacokinetic approach.

METHODS:

A total of 1639 patients with 6427 serum concentrations from 11 Phase 1b, 2 and 3 clinical trials in patients with various cancer indications were included in the analysis. Ramucirumab was administered as an intravenous infusion over 1 h at 8 mg kg-1 every 2 weeks or 10 mg kg-1 every 3 weeks. A series of pharmacostatistical models were developed to describe the concentration data. The best model was used to evaluate patient factors for their effect on ramucirumab pharmacokinetics.

RESULTS:

The pharmacokinetics of ramucirumab were well characterized by a two-compartment model. Mean population estimates of clearance, volume of distribution and half-life for a typical 68-kg patient were 0.0148 l h-1 , 5.30 l and 13.4 days, respectively. A modest relationship was observed between body weight and ramucirumab disposition; clearance and central compartment volume increased with body weight. No other patient characteristics were shown to influence the disposition of ramucirumab in this patient population.

CONCLUSIONS:

The final model adequately described the concentration-time profile of ramucirumab in patients with a range of cancer indications. The model confirmed that a weight-normalized dosing regimen is appropriate for ramucirumab therapy. Dose adjustment was not required for patients with mild to moderate renal impairment or mild hepatic impairment.

• Authors: Lisa O'Brien, Paul Westwood, Ling Gao, Michael Heathman
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 83 Issue 12 Pg. 2741-2751 (12 2017) ISSN: 1365-2125 [Electronic] England
• PMID: 28833321 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological

Topics

• Antibodies, Monoclonal (administration & dosage, adverse effects, blood, pharmacokinetics)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological (administration & dosage, adverse effects, blood, pharmacokinetics)
• Area Under Curve
• Clinical Trials as Topic
• Half-Life
• Humans
• Infusions, Intravenous
• Metabolic Clearance Rate
• Models, Biological
• Neoplasms (blood, drug therapy)
• Treatment Outcome
• Ramucirumab