WCLC 2025 - Posters & ePosters-EP.12.05 The Effect of a Dutch Breakfast on the Exposure of Alectinib Using a Microtracer Approach: A Proof-Of-Concept Study

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This proof-of-concept study investigated the effect of a typical Dutch breakfast on the pharmacokinetics (PK) of alectinib, an ALK inhibitor used in ALK-positive non-small cell lung cancer (NSCLC) patients. Previous food effect studies used a high-calorie, high-fat breakfast that may not represent standard European meals like those in the Netherlands, and traditional studies impose a high burden on patients. This study explored a microtracer approach using a deuterium-labeled variant of alectinib (2H6-alectinib), which is structurally identical except for six hydrogen atoms replaced with deuterium, enabling sensitive PK analysis with minimal patient burden.<br /><br />A prospective, single-center, open-label, crossover design enrolled ten patients receiving the standard 600 mg twice-daily alectinib regimen. Each patient received a microdose (100 µg) of 2H6-alectinib on two occasions: once following a fasted state and once after a standardized Dutch breakfast containing approximately 320–392 kcal and 7.5–7.8 g of fat. A population pharmacokinetic model assessed the relative oral bioavailability (F), area under the plasma concentration-time curve (AUC), and maximum plasma concentration (Cmax). In total, 140 blood samples measuring both labeled and unlabeled drug concentrations were analyzed.<br /><br />Results showed that the Dutch breakfast significantly increased the relative bioavailability, AUC, and Cmax of the microtracer 2H6-alectinib, indicating a positive food effect on alectinib exposure. However, no change was observed in the PK of the unlabeled alectinib in this study. The mean transit time (MTT) to reach systemic circulation was also evaluated. The microtracer method proved feasible, offering the advantage of only requiring two drug administrations under controlled food conditions and a short sampling period, which reduces patient burden compared to conventional studies.<br /><br />In conclusion, the study demonstrates that a standard Dutch breakfast enhances alectinib exposure and validates the microtracer approach as an effective, low-burden method to study food effects on drug pharmacokinetics.

Asset Subtitle

Ma Ida Mohmaed Ali

Meta Tag

Speaker Ma Ida Mohmaed Ali

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

alectinib

ALK inhibitor

non-small cell lung cancer

pharmacokinetics

food effect

Dutch breakfast

microtracer approach

deuterium-labeled alectinib

bioavailability

population pharmacokinetic model