| Title: |
First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial |
| Authors: |
Fizazi, K; Azad, AA; Matsubara, N; Carles, J; Fay, AP; De Giorgi, U; Joung, JY; Fong, PCC; Voog, E; Jones, RJ; Shore, ND; Dunshee, C; Zschäbitz, S; Oldenburg, J; Ye, D; Lin, X; Healy, CG; Di Santo, N; Laird, AD; Zohren, F; Agarwal, N |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2024 |
| Collection: |
The University of Liverpool Repository |
| Description: |
Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; N = 805 (169 were HRR-deficient)), followed by an HRR-deficient-only cohort (cohort 2; N = 230). We present results from the alpha-controlled primary analysis for the combined HRR-deficient population (N = 399). Patients were randomized in a 1:1 ratio to talazoparib or placebo, plus enzalutamide. The primary endpoint, radiographic progression-free survival, was met (median not reached at the time of the analysis for the talazoparib group versus 13.8 months for the placebo group; hazard ratio, 0.45; 95% confidence interval, 0.33 to 0.61; P < 0.0001). Data for overall survival, a key secondary endpoint, are immature but favor talazoparib (hazard ratio, 0.69; 95% confidence interval, 0.46 to 1.03; P = 0.07). Common adverse events in the talazoparib group were anemia, fatigue and neutropenia. Combining talazoparib with enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC harboring HRR gene alterations, supporting talazoparib plus enzalutamide as a potential first-line treatment for these patients. ClinicalTrials.gov Identifier: NCT03395197 . |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1078-8956 |
| Relation: |
Collapse authors list. Fizazi, K orcid:0000-0002-6068-9474 , Azad, AA orcid:0000-0001-7350-5622 , Matsubara, N, Carles, J, Fay, AP, De Giorgi, U, Joung, JY, Fong, PCC, Voog, E, Jones, RJ orcid:0000-0001-5608-001X et al (show 11 more authors) , Shore, ND, Dunshee, C, Zschäbitz, S, Oldenburg, J, Ye, D orcid:0000-0003-4974-3780 , Lin, X, Healy, CG, Di Santo, N, Laird, AD, Zohren, F and Agarwal, N orcid:0000-0003-1076-0428 (2024) First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial Nature Medicine, 30 (1). pp. 257-264. ISSN 1078-8956, 1546-170X |
| DOI: |
10.1038/s41591-023-02704-x |
| Availability: |
https://livrepository.liverpool.ac.uk/3178571/; https://doi.org/10.1038/s41591-023-02704-x |
| Accession Number: |
edsbas.DFFDF39B |
| Database: |
BASE |