Journal Article

Feasibility and efficacy of therapeutic drug monitoring of abiraterone in metastatic castration resistant prostate cancer patients

Bergman, Andries M., Meertens, Marinda, de Feijter, Jeantine M., Kordes, Sil, van der Kleij, Maud B. A., Groenland, Stefanie L., Huitema, Alwin D. R., Steeghs, Neeltje

2025

Overview

Previous studies demonstrated better outcomes for mCRPC (metastatic castration resistant prostate cancer) patients with higher abiraterone exposure (minimal plasma concentration (C ) > 8.4 ng/mL), but around 40% of patients experience exposure below this target. Pharmacokinetic (PK)-guided interventions following Therapeutic Drug Monitoring (TDM) could optimise exposure and outcomes. We aimed to evaluate the feasibility and effect on treatment outcomes of abiraterone TDM. Patients with low exposure levels (Low-group, C  < 8.4 ng/mL) got a PK-guided intervention. We compared exposure, adverse event (AE) incidence, time on treatment (ToT) and Prostate-Specific Antigen response rate (PSArr) between the Low-group and Adequate-group. We included 167 mCRPC patients, with 56 in the Adequate-group and 111 in the Low-group. Interventions were successful 86% of the time. Exposure between groups became corresponding (Low-group: 7.95 to 20.5 ng/mL, Adequate-group: 20.8 ng/mL, p = 0.72) with comparable AE incidence (17% vs. 23%, p = 0.4). Median ToT and PSArr were similar (351 vs. 379 days, p = 0.35; 61.3% vs. 67.9%, p = 0.51). PK-guided interventions improved above target exposure from 33.5% to 81.4% of patients without additional AEs. While historically, low exposure patients had significantly shorter survival, PK-guided interventions eliminated this disparity. As interventions are effective, low-cost and safe, TDM for abiraterone should be considered to enhance treatment outcomes.

• Publisher: Nature Publishing Group,Nature Publishing Group UK
• Subject: Aged / Aged, 80 and over / Androstenes - administration & dosage / Androstenes - adverse effects / Androstenes - pharmacokinetics / Androstenes - therapeutic use / Cancer therapies / Castration / Clinical outcomes / Drug Monitoring - methods / Feasibility Studies / Humans / Male / Metastases / Metastasis / Middle Aged / Neoplasm Metastasis / Pharmacokinetics / Precision medicine / Prostate cancer / Prostate-specific antigen / Prostate-Specific Antigen - blood / Prostatic Neoplasms, Castration-Resistant - blood / Prostatic Neoplasms, Castration-Resistant - drug therapy / Prostatic Neoplasms, Castration-Resistant - pathology / Retrospective Studies / Therapeutic drug monitoring / Treatment Outcome