Food effect studies and drug label recommendations: A review of recently approved oncology products.

Abstract

2535 Background: Evaluation of the effect of food on the pharmacokinetics of orally administered oncology drugs is a critical aspect of drug development, as food can mitigate or exacerbate toxicities and can change and influence variability in systemic exposure. Our aim in this review of approved oncology products is to describe the approaches used by sponsors to assess food effect and decide on the final dosing recommendations. Methods: Data for small molecule oncology drugs approved between 2003-2016 was extracted from the clinical pharmacology review in the sponsor’s FDA submission package. Information on food-effect study design, outcomes, intersubject variability, exposure-response relationships for safety, and the label dosing recommendation regarding food was analyzed. Results: Of the 29 drugs analyzed, 19 food effect studies were conducted in healthy volunteers, and 10 were conducted in cancer patients. The ratio of population geometric means between fed and fasted treatments fell outside the 80-125 percent equivalence limit in 55% of compounds for AUC and in 69% of compounds for Cmax. 6 drugs (21%) are recommended to be given with food, 11 drugs (38%) in the fasted state, and 12 drugs (41%) can be dosed regardless of food. Label recommendations appeared to be driven by the exposure-response analysis. 80% of drugs with a fasted label recommendation despite an increase in bioavailability with food had an exposure-response relationship for safety. Conclusions: Optimizing study design by conducting early food effect studies designed to estimate food effect rather than confirming no food effect, and learning the impact of food early may eliminate unnecessary study arms and save sponsors money and time. Furthermore, understanding the potential of food to mitigate or exacerbate toxicities may improve patients’ experience with treatments and has been shown here to be a major driver of the final dosing recommendation regarding food.