Abstract
AbstractTalazoparib, a poly(ADP-ribose) polymerase inhibitor, has demonstrated efficacy in the treatment of advanced breast and prostate cancers in Western populations. This open-label, phase 1 study investigated the pharmacokinetics, safety, and antitumor activity of talazoparib monotherapy in Chinese patients with advanced solid tumors. Molecularly unselected patients (≥18 years) with advanced solid tumors resistant to standard therapy received talazoparib (oral, 1 mg once daily). Primary endpoint was characterization of single-dose and steady-state pharmacokinetics. Secondary endpoints evaluated safety, unconfirmed objective response rate (ORR), and duration of response. The safety population comprised 15 Chinese patients (median [range] age 53.0 [31.0–72.0] years). Single-dose median time to first occurrence of maximum observed concentration was 1.9 h; concentrations then declined with a mean terminal half-life (t1/2) of 67 h. Following multiple dosing, median Tmax was approximately 1.85 h with steady state generally achieved by Day 21. Treatment-related treatment-emergent adverse events (TEAEs) occurred in 86.7% (13/15) of patients (grade 3, 20.0%; grade 4, 13.3%). Two patients (13.3%) experienced serious treatment-related TEAEs. ORR (investigator-assessed) was 6.7% (95% CI: 0.2–31.9); one patient (6.7%) had a partial response. In patients with measurable disease at baseline, the ORR was 9.1% (1/11; 95% CI: 0.2–41.3; duration of response: 114 days); stable disease was achieved by 36.4% (4/11) of patients, and 54.5% (6/11) progressed by data cut-off. In Chinese patients with advanced solid tumors, the pharmacokinetic profile of talazoparib monotherapy (1 mg/day) was consistent with other patient populations. TEAEs were generally manageable with no unexpected safety findings. (ClinicalTrials.gov: NCT04635631 [prospectively registered November 19, 2020])
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Pharmacology,Oncology
Reference23 articles.
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660
2. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2020) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. World Health Organization. https://gco.iarc.fr/today . Accessed December 13, 2022
3. Cao W, Chen HD, Yu YW, Li N, Chen WQ (2021) Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl) 134:783–791. https://doi.org/10.1097/cm9.0000000000001474
4. Lord CJ, Ashworth A (2017) PARP inhibitors: Synthetic lethality in the clinic. Science 355:1152–1158. https://doi.org/10.1126/science.aam7344
5. Javle M, Curtin NJ (2011) The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy. Ther Adv Med Oncol 3:257–267. https://doi.org/10.1177/1758834011417039