RT Journal Article
T1 Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses.
A1 Mehra, Niven
A1 Fizazi, Karim
A1 de Bono, Johann S
A1 Barthélémy, Philippe
A1 Dorff, Tanya
A1 Stirling, Adam
A1 Machiels, Jean-Pascal
A1 Bimbatti, Davide
A1 Kilari, Deepak
A1 Dumez, Herlinde
A1 Buttigliero, Consuelo
A1 van Oort, Inge M
A1 Castro, Elena
A1 Chen, Hsiang-Chun
A1 Di Santo, Nicola
A1 DeAnnuntis, Liza
A1 Healy, Cynthia G
A1 Scagliotti, Giorgio V
K1 BRCA
K1 PARP inhibitor
K1 castration-resistant prostatic cancer
K1 talazoparib
AB The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib. Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs. In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]). Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC. NCT03148795.
YR 2022
FD 2022
LK http://hdl.handle.net/10668/19827
UL http://hdl.handle.net/10668/19827
LA en
DS RISalud
RD Apr 12, 2025