Precision medicine in non-small cell lung cancer: Improving dosing strategies

Abstract

In the current era of precision medicine in oncology, the tailoring of treatment of patients on the (molecular) characteristics of the tumor is widely performed. However, for many drugs, the full spectrum of precision medicine is not yet implemented in routine practice. The doses of drugs are still mostly based on the one-size-fits-all dosing approach. Nonetheless, the clinical pharmacology of these drugs suggests and warrants for the optimization of the current strategies. With the high incidence of non-small cell lung cancer (NSCLC), even minor improvements in the current dosing of the therapeutic options for this indication could have a high impact on the efficacy, toxicity and costs of treatment and the quality of life. In this thesis, parts of the knowledge gaps on dose optimizations for several therapeutic options of NSCLC are elucidated. The aim of Part I, Chapter 1 was to discuss the rationale of dose optimizations for the smallmolecule inhibitors (SMIs), cytostatic agents and monoclonal antibodies in the treatment of NSCLC. Part II described the rationale and impact of inhibition of the metabolic enzymes of SMIs and cytostatic agents. Predictors of pharmacokinetics of the therapeutic options for NSCLC were described and evaluated in Part III. Part IV addressed the relationships between exposure to drugs and the efficacy and/or toxicity of the therapy. In conclusion, this thesis described several studies, which aimed to improve the dosing strategies for the treatment of NSCLC. It was concluded that for many drugs a rationale for dose optimization is present. The landscape of the therapeutic window should first be assessed, followed by the identification of predictors for the systemic exposure of the drug. Finally, based on this information, efforts could be made to ensure that the individual patient is dosed the most optimal dosing with regard to efficacy, toxicity, quality of life and financial burden. Implementation of these considerations might prove valuable in the quest to optimize precision medicine in clinical practice.