Dose Regimen Rationale for Panitumumab in Cancer Patients: To Be Based on Body Weight or Not
Authors Liao MZ, Berkhout M, Prenen H, Dutta S, Upreti VV
Received 15 May 2020
Accepted for publication 7 July 2020
Published 31 July 2020 Volume 2020:12 Pages 109—114
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Arthur Frankel
Michael Z Liao, 1 Marloes Berkhout, 2 Hans Prenen, 3 Sandeep Dutta, 4 Vijay V Upreti 1
1Clinical Pharmacology, Modeling & Simulation, Amgen Inc., South San Francisco, CA, USA; 2Medical Development, Amgen B.V, Breda, the Netherlands; 3Department of Medical Oncology, University Hospital Antwerp, Edegem, Belgium; 4Clinical Pharmacology, Modeling & Simulation, Amgen Inc., Thousand Oaks, CA, USA
Correspondence: Vijay V Upreti
Clinical Pharmacology, Modeling & Simulation, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA
Fax +1 650-837-9421
Introduction: Body weight can affect exposure, safety and efficacy of antibody-based therapies; sometimes these effects may not be clinically relevant. Panitumumab is approved for wild-type RAS metastatic colorectal cancer, using a body weight–based dosing regimen. Recently, a report cited fixed-dose usage of panitumumab, rather than approved body weight–based dosing. The current work evaluates optimal dosing regimen scientifically based on clinical data, modeling and simulation. Herein, we assessed the effect of fixed and body weight–based dosing on panitumumab pharmacokinetics to determine which approach resulted in the least interpatient pharmacokinetic variability.
Patients and Methods: From the Vectibix program, 352 patients enrolled in three studies were evaluated; they had received panitumumab (body weight–based dose: 6 mg/kg every 2 weeks) and had pharmacokinetic (maximum serum [Cmax] and trough [Cmin] concentrations) and body weight data available. Additionally, concentration-time profiles at fixed (480 mg) and body weight–based doses (6 mg/kg) were simulated using a population pharmacokinetics model developed from 1200 patients.
Results: After administration of panitumumab 6 mg/kg, Cmax and Cmin increased with increasing body weight; the mean Cmax and Cmin for patients weighing < 65 kg (lower quartile) were 23% and 30% lower, respectively, than for those weighing > 88 kg (upper quartile). The simulated area under the concentration–time curve (AUC) data also indicated that overall panitumumab exposure increased with increasing body weight for the body weight–based regimen. When AUC was simulated for a fixed dose (480 mg), the opposite effect was observed. Over the range of body weights, interpatient variability in simulated AUC was lower for the weight-based dose (29%) than for the fixed dose (34%).
Conclusion: Results demonstrate that the weight-based dose (6 mg/kg) reduced variability in panitumumab exposure across the range of body weights compared with the fixed-dose approach, indicating that a body weight–based approach is the recommended patient dosing strategy.
Keywords: panitumumab, pharmacokinetics, dose-exposure relationship, body weight, area under the curve, colorectal neoplasms
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