Consideration on Food Effect Studies for Anticancer Drugs Approved in Japan Between 2001 and 2022.

In developing a new drug, studies to evaluate the food effect (FE) on the drug's pharmacokinetics (FE studies) are generally conducted in healthy subjects in the early stages of clinical development. Conversely, for anticancer drugs, which have many adverse effects, it is assumed that FE studies cannot be conducted in healthy subjects. However, many unknowns exist about how FE on oral anticancer drugs is examined in clinical development. In this study, we aimed to examine the characteristics of conducting FE studies on anticancer drugs approved in Japan to date. Between 2001 and 2022, 70 new oral anticancer drugs had been approved in Japan. Of the 70 drugs, 67 (95.7%) were subjected to FE studies. Ninety-five FE studies were conducted on these 67 oral anticancer drugs. Sixty-three studies (66.3%) were conducted on (1) healthy subjects. Most studies were (2) single-dose, (3) single-dosage arm, (4) nonrandomized, (5) crossover, and (6) with a sample size of 11-30 cases. In addition, 80 (84.2%) of the FE studies were conducted ex-Japan, not in Japan. Furthermore, the results of the chi-square test indicated that "(1) drugs using ex-Japan clinical data" "(2) drugs other than cytotoxic anticancer drugs" "(3) drugs developed ex-Japan" and "(4) drugs with > 100 cases in pivotal trials" were more likely to be subjected to FE studies. In conclusion, in FE studies, clinical trials in healthy subjects rather than patients have already been conducted in response to changes in the modality from cytotoxic drugs to molecular targeted drugs and immune checkpoint inhibitors.