TY - JOUR
T1 - Feasibility and efficacy of therapeutic drug monitoring of abiraterone in metastatic castration resistant prostate cancer patients
T2 - Clinical Studies
AU - van der Kleij, Maud B.A.
AU - Meertens, Marinda
AU - on behalf of the Dutch Pharmacology Oncology Group (DPOG)
AU - Groenland, Stefanie L.
AU - Kordes, Sil
AU - Bergman, Andries M.
AU - de Feijter, Jeantine M.
AU - Huitema, Alwin D.R.
AU - Steeghs, Neeltje
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/2/11
Y1 - 2025/2/11
N2 - Background:Previous studies demonstrated better outcomes for mCRPC (metastatic castration resistant prostate cancer) patients with higher abiraterone exposure (minimal plasma concentration (Cmin) > 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. Methods: Patients with low exposure levels (Low-group, Cmin < 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. Results: 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). Conclusions: 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.
AB - Background:Previous studies demonstrated better outcomes for mCRPC (metastatic castration resistant prostate cancer) patients with higher abiraterone exposure (minimal plasma concentration (Cmin) > 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. Methods: Patients with low exposure levels (Low-group, Cmin < 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. Results: 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). Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85219185605&partnerID=8YFLogxK
U2 - 10.1038/s41416-025-02954-1
DO - 10.1038/s41416-025-02954-1
M3 - Article
C2 - 39934337
AN - SCOPUS:85219185605
SN - 0007-0920
VL - 132
SP - 635
EP - 642
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -
