Background: With the increasing efficacy and survival rates, the use of antitumour drugs has evolved into chronic therapies. Pembrolizumab is a monoclonal antibody currentlly used as first-line treatment of metastatic non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberration. The approved intravenous dosing regimen is 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months without disease progression. Responding patients, however, may remain on drug therapy for longer periods.
Objectives: The primary objective of this project is to evaluate the feasibility of alternative dosing regimens, including intermittent therapy with pembrolizumab. Using published literature data on the pharmacokinetics and pharmacodynamics along with patient records, systemic exposure will be simulated for a range of dosing regimens for pembrolizumab.
Methods: Published data on pharmacokinetics, efficacy and safety will be reviewed and digitised using a model‐based meta‐analytical approach. Available population pharmacokinetic models will be used to characterise pembrolizumab exposure across different dosing scenarios and assess the most suitable regimen for chronic interventions.
Skills and competencies: In addition to data manipulation (statistical summaries and data visualisation), basic knowledge in (bio) statistics and clinical pharmacology will be required for the successful implementation of the research proposal. Software programs to be used during the project include R and NONMEM v.7.3.