Use of a Population Pharmacokinetic Approach for the Clinical Development of a Fixed‐Dose Subcutaneous Formulation of Trastuzumab
Open accessAbstract
A new subcutaneous (s.c.) trastuzumab formulation provides savings in terms of time and is preferred by patients and health care professionals relative to standard intravenous (i.v.) administration due to simpler and more rapid administration (2–5 minutes). Selection of the s.c. dose was based on a pharmacokinetic bridging approach that aimed to achieve noninferior trastuzumab serum trough concentrations ( C trough ) vs. reference i.v. administration. Using population modeling and simulation, we showed that a fixed 600‐mg trastuzumab s.c. dose, administered thrice‐weekly (Q3W) without a loading dose, would provide C trough (predose Cycle 8) and area under the time–concentration curve (AUC 0–21 days , Cycle 7) at least as high as Q3W i.v. administration. The model was retrospectively validated using observed pharmacokinetic data from an independent phase III study of (neo)adjuvant trastuzumab (HannaH). These results provide a strong pharmacokinetic rationale for the trastuzumab s.c. 600‐mg fixed dose, supported by the noninferior efficacy of this regimen vs. reference i.v. administration. CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e87; doi: 10.1038/psp.2013.63 ; advance online publication 2 January 2014
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Population pharmacokinetic modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of monoclonal antibodies could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment.
“Furthermore, population pharmacokinetic (PopPK) modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of mAbs could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment [20–23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [22]
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References 24 · Cited by 28
Research works printed but not linked: 2
- Pivot X. Patient preference for subcutaneous versus intravenous adjuvant trastuzumab: results of the PrefHer study. 13th St Gallen International Breast Cancer Conference, St Gallen, Switzerland, 13–16 March 2013.
- De Cock E. Time savings with trastuzumab subcutaneous vs. intravenous administration: a time and motion study. 13th St Gallen International Breast Cancer Conference, St Gallen, Switzerland, 13–16 March 2013.
- Authors
- Hourcade‐Potelleret, F., Lemenuel‐Diot, A., McIntyre, C., Brewster, M., Lum, B., & Bittner, B.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- Roche (United Kingdom) (GB)
- Genentech (US)
- Corresponding author
- Bittner, B
- Venue
- CPT: Pharmacometrics & Systems Pharmacology
- Publisher
- Wiley
- Published
- 2014-01
- Volume
- 3
- Issue
- 1
- Pages
- 1-9
- ISSN
- 2163-8306 (ISSN-L)
- PMC
- PMC3910009
- OpenAlex
- W1987625267
- Cited by
- 28
- References
- 24
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 3 · 2014: 2
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- F. Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- trastuzumab, subcutaneous administration, fixed-dose formulation, population pharmacokinetic model, non-inferiority, trough concentration, area under the concentration-time curve
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