Influence of Food With Different Fat Concentrations on Alectinib Exposure : A Randomized Crossover Pharmacokinetic Trial

Background: Alectinib is the keystone treatment in advanced ana-plastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). An exposure-response threshold of 435 ng/mL has recently been established, albeit 37% of patients do not reach this threshold. Alectinib is orally administered, and absorption is largely influenced by food. Hence, further investigation into this relationship is needed to optimize its bioavailability.Patients and Methods: In this randomized 3-period crossover clinical study in ALK+ NSCLC, alectinib exposure was compared among patients with different diets. Every 7 days, the first alectinib dose was taken with either a continental breakfast, 250-g of low-fat yogurt, or a self-chosen lunch, and the second dose was taken with a self-chosen dinner. Sampling for alectinib exposure (Ctrough) was performed at day 8, just prior to alectinib intake, and the relative differ-ence in Ctrough was compared.Results: In 20 evaluable patients, the mean Ctrough was 14% (95% CI, -23% to -5%; P=.009) and 20% (95% CI, -25% to -14%; P<.001) lower when taken with low-fat yo-gurt compared with a continental breakfast and a self-chosen lunch, respectively. Administration with a self-chosen lunch did not change exposure compared with a continental breakfast (+7%; 95% CI, -2% to +17%; P=.243). In the low-fat yogurt period, 35% of patients did not reach the threshold versus 5% with the other meals (P<.01).Conclusions: Patients and physicians should be warned for a detri-mental food-drug interaction when alectinib is taken with low-fat yo-gurt, because it results in a clinically relevant lower alectinib exposure. Intake with a self-chosen lunch did not change drug exposure and could be a safe and patient-friendly alternative.

Automated summary

This study investigated the influence of different diets on the exposure of alectinib in ALK+ NSCLC patients. The results showed that low-fat yogurt significantly reduced the exposure of alectinib compared to other diets, while a self-chosen lunch did not change the exposure. Therefore, patients and physicians should be cautious about the food-drug interaction between alectinib and low-fat yogurt, as it may lead to reduced exposure.