Reducing the Burden of Interaction Studies in Cancer Patients Using a Stable Isotopically Labeled Microtracer: A...

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Oncology
• Clinical Pharmacology

Background:

• Traditional drug-food interaction studies for oral anticancer agents impose a substantial patient burden.
• Stable isotopically labeled microtracers offer a patient-friendly alternative for assessing food effects on drug absorption.

Purpose of the Study:

• To evaluate the feasibility of using a stable isotopically labeled microtracer (2H6-alectinib) to study food effects on alectinib pharmacokinetics.
• To assess the impact of a standardized Dutch breakfast on the bioavailability and exposure of alectinib in patients with ALK-positive non-small cell lung cancer.

Main Methods:

• A prospective, single-center, open-label, crossover study was conducted in patients receiving alectinib.
• Patients received 2H6-alectinib microtracer with a standardized breakfast (fed state) and after overnight fasting (fasted state).
• Population pharmacokinetic modeling was used to assess the effect of food on relative bioavailability (F) and mean transit time (MTT).

Main Results:

• Mean transit time was 3.14 hours in the fed state.
• Compared to the fed state, MTT and F were 28% and 35% lower, respectively, in the fasted state.
• The geometric mean ratio (fed vs. fasted) for area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) was 1.52 and 1.42, respectively, indicating increased alectinib exposure when taken with food.

Conclusions:

• The intake of a Dutch breakfast significantly increases total alectinib exposure in patients.
• The microtracer approach is feasible and effective in studying drug-food interactions, demonstrating a reduced patient burden compared to traditional methods.
• This method provides valuable insights into alectinib pharmacokinetics and food effects for optimizing treatment regimens.