van der Kleij Maud B A, Meertens Marinda, Groenland Stefanie L, Kordes Sil, Bergman Andries M, de Feijter Jeantine M, Huitema Alwin D R, Steeghs Neeltje
Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Br J Cancer. 2025 Apr;132(7):635-642. doi: 10.1038/s41416-025-02954-1. Epub 2025 Feb 11.
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.
既往研究表明，阿比特龙暴露量较高（最低血浆浓度（C）＞8.4 ng/mL）的转移性去势抵抗性前列腺癌（mCRPC）患者预后更好，但约40%的患者暴露量低于该目标值。治疗药物监测（TDM）后的药代动力学（PK）指导干预可优化暴露量及预后。我们旨在评估阿比特龙TDM的可行性及其对治疗预后的影响。
暴露水平较低的患者（低暴露组，C＜8.4 ng/mL）接受PK指导干预。我们比较了低暴露组和充足暴露组之间的暴露量、不良事件（AE）发生率、治疗时间（ToT）和前列腺特异性抗原反应率（PSArr）。
我们纳入了167例mCRPC患者，其中充足暴露组56例，低暴露组111例。干预成功率为86%。两组间的暴露量变得相当（低暴露组：7.95至20.5 ng/mL，充足暴露组：20.8 ng/mL，p = 0.72），AE发生率相当（17%对23%，p = 0.4）。ToT中位数和PSArr相似（351天对379天，p = 0.35；61.3%对67.9%，p = 0.51）。
PK指导干预使达到目标暴露量的患者比例从33.5%提高到81.4%，且未增加AE。从历史数据来看，低暴露患者的生存期显著较短，但PK指导干预消除了这种差异。由于干预有效、成本低且安全，应考虑对阿比特龙进行TDM以提高治疗效果。
