Dose rationalization of pembrolizumab and nivolumab using pharmacokinetic modeling and simulation and cost analysis.
AffiliationCentre for Applied Pharmacokinetic Research, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester
MetadataShow full item record
AbstractPembrolizumab and nivolumab are highly selective anti-programmed cell death 1 (PD-1) antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies (mAbs). The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose, and pharmacokinetic (PK)-based methods. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and PK-derived strategies were -15%, -25%, + 7%, and -16% for pembrolizumab and -8%, -6%, and -10% for band, fixed, and PK-derived strategies for nivolumab, respectively. Relative to mg/kg doses, the median exposures were -1.0%, -4.6%, + 27.1%, and +3.0% for band, fixed 150 mg, fixed 200 mg, and PK-derived strategies, respectively, for pembrolizumab and -3.1%, + 1.9%, and +1.4% for band, fixed 240 mg, and PK-derived strategies, respectively, for nivolumab. Significant wastage can be reduced by alternative dosing strategies without compromising exposure and efficacy.
CitationDose rationalization of pembrolizumab and nivolumab using pharmacokinetic modeling and simulation and cost analysis. 2017, Clin Pharmacol Ther
JournalClinical Pharmacology and Therapeutics
- Switch to anti-programmed cell death protein 1 (anti-PD-1) fixed-dose regimen: What is the economic impact?
- Authors: Bayle A, Besse B, Annereau M, Bonastre J
- Issue date: 2019 May
- Evaluation of dosing strategy for pembrolizumab for oncology indications.
- Authors: Freshwater T, Kondic A, Ahamadi M, Li CH, de Greef R, de Alwis D, Stone JA
- Issue date: 2017
- Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor.
- Authors: Belum VR, Benhuri B, Postow MA, Hellmann MD, Lesokhin AM, Segal NH, Motzer RJ, Wu S, Busam KJ, Wolchok JD, Lacouture ME
- Issue date: 2016 Jun
- Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma.
- Authors: Ivashko IN, Kolesar JM
- Issue date: 2016 Feb 15
- Model-Based Characterization of the Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in Advanced Solid Tumors.
- Authors: Ahamadi M, Freshwater T, Prohn M, Li CH, de Alwis DP, de Greef R, Elassaiss-Schaap J, Kondic A, Stone JA
- Issue date: 2017 Jan