Exposure-safety analyses of talazoparib in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial

Wang, Y; Hadigol, M; Lincha, VR; Hoffman, J; Azad, AA; Agarwal, N; Matsubara, N; Zohren, F; DeAnnuntis, L; Wang, DD

Author(s): Wang, Y; Hadigol, M; Lincha, VR; Hoffman, J; Azad, AA; Agarwal, N; Matsubara, N; Zohren, F; DeAnnuntis, L; Wang, DD;
Details: Publication Year 2026-06-04,Volume 53,Issue #4,Page 30
Journal Title: Journal of Pharmacokinetics and Pharmacodynamics
Publication Type: Research article
Abstract: The TALAPRO-2 trial (NCT03395197) showed that the addition of talazoparib, a potent PARP inhibitor, to enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC. Due to adverse events (AEs), approximately 62% of patients experienced dose interruption and 53% of patients experienced dose reduction of talazoparib in TALAPRO-2 trial. Hematologic AEs such as anemia, thrombocytopenia, and neutropenia were the most common AEs leading to dose interruptions or reductions. We investigated the relationship between talazoparib exposure as well as baseline patients/disease characteristics and Grade ≥ 3 anemia, thrombocytopenia, and neutropenia using graphical examination and Cox proportional hazard models. The results indicated that higher talazoparib exposure, C(avg, t), was associated with a higher risk of Grade ≥ 3 anemia, thrombocytopenia, and neutropenia. Additionally, among the other baseline factors, we observed that higher risk of all tested safety endpoints was associated with lower baseline hemoglobin. In addition, higher risk of anemia was associated with lower baseline body weight and higher baseline lactate dehydrogenase. Higher risk of neutropenia was associated with lower baseline absolute neutrophil count and lower baseline body weight. These findings support the proposed dose modification algorithm as an effective approach for management of AEs.
Publisher: Springer Nature
Keywords: Aged; Humans; Male; Middle Aged; Anemia/chemically induced; *Antineoplastic Combined Chemotherapy Protocols/adverse effects/administration &; dosage/pharmacokinetics/therapeutic use; *Benzamides/administration & dosage/adverse effects; Dose-Response Relationship, Drug; Neutropenia/chemically induced; *Nitriles/administration & dosage/adverse effects; *Phenylthiohydantoin/administration & dosage/analogs & derivatives/adverse; effects/pharmacokinetics; *Phthalazines/administration & dosage/adverse effects/pharmacokinetics; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage/adverse; effects/pharmacokinetics; Progression-Free Survival; *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology; Thrombocytopenia/chemically induced; Exposure metrics; Exposure-response; Talazoparib; Time-varying exposure; mCRPC
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1007/s10928-026-10038-7
Open Access at Publisher's Site: https://doi.org/10.1007/s10928-026-10038-7
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-06-23 03:42:09

Last Modified: 2026-06-23 03:42:14