First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer

• Verfasst von: Fizazi, Karim [VerfasserIn]
• Verfasst von: Azad, Arun A. [VerfasserIn]
• Verfasst von: Matsubara, Nobuaki [VerfasserIn]
• Verfasst von: Carles, Joan [VerfasserIn]
• Verfasst von: Fay, Andre P. [VerfasserIn]
• Verfasst von: Giorgi, Ugo de [VerfasserIn]
• Verfasst von: Joung, Jae Young [VerfasserIn]
• Verfasst von: Fong, Peter C. C. [VerfasserIn]
• Verfasst von: Voog, Eric [VerfasserIn]
• Verfasst von: Jones, Robert J. [VerfasserIn]
• Verfasst von: Shore, Neal D. [VerfasserIn]
• Verfasst von: Dunshee, Curtis [VerfasserIn]
• Verfasst von: Zschäbitz, Stefanie [VerfasserIn]
• Verfasst von: Oldenburg, Jan [VerfasserIn]
• Verfasst von: Ye, Dingwei [VerfasserIn]
• Verfasst von: Lin, Xun [VerfasserIn]
• Verfasst von: Healy, Cynthia G. [VerfasserIn]
• Verfasst von: Di Santo, Nicola [VerfasserIn]
• Verfasst von: Laird, A. Douglas [VerfasserIn]
• Verfasst von: Zohren, Fabian [VerfasserIn]
• Verfasst von: Agarwal, Neeraj [VerfasserIn]
• Titel: First-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer
• Titelzusatz: the phase 3 TALAPRO-2 trial
• Verf.angabe: Karim Fizazi, Arun A. Azad, Nobuaki Matsubara, Joan Carles, Andre P. Fay, Ugo De Giorgi, Jae Young Joung, Peter C.C. Fong, Eric Voog, Robert J. Jones, Neal D. Shore, Curtis Dunshee, Stefanie Zschäbitz, Jan Oldenburg, Dingwei Ye, Xun Lin, Cynthia G. Healy, Nicola Di Santo, A. Douglas Laird, Fabian Zohren & Neeraj Agarwal
• E-Jahr: 2024
• Jahr: January 2024
• Umfang: 8 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar: 4. Dezember 2023, Artikelversion: 31. Januar 2024 ; Gesehen am 19.02.2024
• Titel Quelle: Enthalten in: Nature medicine
• Ort Quelle: New York, NY : Nature America Inc., 1995
• Jahr Quelle: 2024
• Band/Heft Quelle: 30(2024), 1 vom: Jan., Seite 257-264
• ISSN Quelle: 1546-170X
• DOI: doi:10.1038/s41591-023-02704-x
• Datenträger: Online-Ressource
• Sprache: eng
• Bibliogr. Hinweis: Ergänzung: Fizazi, Karim: Publisher correction
• Sach-SW: Prostate cancer
• K10plus-PPN: 1881104362

Abstract

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.