Role of pharmacokinetic modeling and simulation in precision dosing of anticancer drugs

The prospect of precision dosing in oncology is attractive for several reasons. Many anticancer drugs display narrow therapeutic indices, where suboptimal therapy may lead to severe patient outcomes. Clinical study participant recruitment is seldom extended beyond the intended patient population, leading to difficulties in patient recruitment in dedicated clinical trials. The high rate of non-responders and high cost of cancer therapy warrant novel solutions to increase clinical effectiveness and cost-benefit, pharmacokinetic (PK) modeling and model-informed precision dosing (MIPD) can help to maximize these. PK modeling provides a quantitative framework to account for inter-individual variability in drug exposure, the influence of covariates and extrapolation to special populations or drug-drug interactions, using physiologically-based PK (PBPK) modeling. Here we present the current state of PK modeling in precision dosing of anticancer drugs and illustrate its utility, based on an extensive literature review and numerous case examples from both pharmaceutical industry and healthcare focused research. While some great progress has been made in implementing model-informed dosage guidance in the drug label and much research has been carried out to address clinically relevant dosing questions, the uptake of MIPD has been modest in healthcare. The success of PK modeling in industry has been made possible through collaborative efforts between regulators, industry and academia. Collaboration between academia, healthcare and industry, and financial support for research into patient benefit, cost-benefit and clinical effectiveness of these approaches is imperative for wider adaption of PK modeling in precision dosing of anticancer drugs.