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A retrospective examination of the US Food and Drug Administration’s clinical pharmacology reviews of oncology biologics for potential use of therapeutic drug monitoring

Authors Fleisher B, Ait-Oudhia S

Received 2 October 2017

Accepted for publication 3 December 2017

Published 27 December 2017 Volume 2018:11 Pages 113—121


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Brett Fleisher, Sihem Ait-Oudhia

Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA

Background: Biologics have gained traction for use in oncology, but have demonstrate clinical variability for efficacy and safety. Therapeutic drug monitoring (TDM) can benefit patients’ outcomes from a biologic therapy when the latter has a defined therapeutic window. A clinically relevant therapeutic window may exist for biologics with established exposure-response (E–R) relationships for efficacy and/or safety and a documented maximum tolerated dose (MTD). Additionally, the inter-individual variability (IIV) on the clearance (CL) parameter could determine risks for patients falling outside the proposed therapeutic window.
Materials and methods: The US Food and Drug Administration (FDA)-approved oncology biologics between 2005–2016 were reviewed via FDA “Purple Book” (FDA-repository for licensed biologics). Data were extracted from biologics’ pharmacokinetic models available on the clinical pharmacology reviews published on the FDA-Approved Drug Products website. Evaluated features for biologics with established E–R relationships for efficacy and/or safety and MTD include an IIV for the CL and various other covariates including demographic factors, disease factors, blood chemistry, or immunogenicity.
Results: Five therapies were identified with documented E–R relationships for both efficacy and safety including, Yervoy®(ipilimumab), Zaltrap® (ziv-aflibercept), Portrazza® (necitumumab), Adcetris® (brentuximab-vedotin), and Blincyto® (blinatumomab). The corresponding IIV on CL were: 34%, 33%, 29%, 47%, and 97%, respectively. Among the five therapies, only three had defined MTD including, brentuximab-vedotin, necitumumab, and blinatumomab.
Conclusion: Of the medications examined, blinatumomab was identified as the anticancer drug with the most available information for the establishment of TDM, and hence, may benefit through the use of TDM to optimize effectiveness and minimize patients’ toxicity . The approach used here may provide a generalizable framework to retrospectively identify anticancer biologics with high IIV that may benefit from TDM to improve patients’ clinical outcome.

Keywords: therapeutic drug monitoring, oncology biologics, blinatumomab

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