Concomitant intake of abiraterone and food to increase pharmacokinetic exposure: Real-life data from a therapeutic drug monitoring program.

Abstract

3117 Background: Abiraterone acetate is registered for the treatment of metastatic castration resistant prostate cancer. Pharmacokinetic (PK) exposure has been linked to efficacy, since patients with Cmin ≥ 8.4 ng/mL have a significantly longer progression free survival compared to patients with a Cmin below this threshold (7.4 vs. 12.2 months, p = 0.044) (Carton, 2017). At the recommended fixed dose of 1000 mg QD administered in a modified fasting state, 35% of patients do not reach this efficacy threshold (Carton, 2017), providing a strong rationale for therapeutic drug monitoring (TDM). Since a clinically relevant food effect has been established, concomitant intake of abiraterone and food could offer a cost-neutral solution in case of low exposure (Chi, 2015). This study aims to evaluate whether PK-guided abiraterone dosing is feasible and results in an increased proportion of patients with concentrations above the target. Methods: Patients starting regular treatment with abiraterone were included. PK sampling occurred 4, 8 and 12 weeks after start of treatment, and every 12 weeks thereafter. Abiraterone concentrations were measured and Cmin was calculated. In case of Cmin < 8.4 ng/mL and acceptable toxicity, a PK-guided intervention was advised. As a first step, concomitant intake of abiraterone and a light meal or a snack was advised. Results: In total, 35 patients were included, of which 18 patients (51%) had at least one Cmin < 8.4 ng/mL. These patients were advised to take abiraterone concomitantly with food, after which Cmin increased significantly from 5.6 (47%) ng/mL [mean (CV%)] to 40.6 (110%) ng/mL (p = 0.006) without additional toxicities. This intervention led to adequate exposure in 15 patients (83%). Seventeen patients had all Cmin levels ≥ 8.4 ng/mL, in these patients mean Cmin was 31.5 (65%) ng/mL. Conclusions: TDM of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted into a significant increase in Cmin and offers a cost-neutral opportunity to optimize treatment for patients with low PK exposure. Up to 100 patients will be included to evaluate the effect of PK-guided abiraterone dosing on treatment efficacy. Clinical trial information: NL6695.