A previous trial involving patients with metastatic prostate cancer that was resistant to androgen pathway modulation (formerly referred to as castration-resistant) showed that adding talazoparib to enzalutamide significantly improved imaging-based progression-free survival and overall survival, with the greatest benefit observed in the cohort with alterations in homologous recombination repair genes.
In this ongoing, phase 3, double-blind trial assessing talazoparib in patients with metastatic androgen pathway modulation-sensitive [APMS] prostate cancer harboring alterations in homologous recombination repair genes, we randomly assigned patients in a 1:1 ratio to receive talazoparib at a dose of 0.5 mg plus enzalutamide at a dose of 160 mg once daily (talazoparib group) or placebo plus enzalutamide at a dose of 160 mg once daily (control group). Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (vs. non-BRCA) mutation status. The primary end point was investigator-assessed imaging-based progression-free survival. The key secondary end point was overall survival.
A total of 300 patients were assigned to the talazoparib group and 299 to the control group. At 3 years, progression-free survival was 77% in the talazoparib group and 56% in the control group (hazard ratio for disease progression or death, 0.48; 95% confidence interval [CI], 0.36 to 0.65; P<0.001). In this interim analysis, overall survival at 3 years was 78% in the talazoparib group and 72% in the control group (hazard ratio for death, 0.77; 95% CI, 0.56 to 1.04). Serious adverse events were reported in 42% and 32% of the patients in the talazoparib group and the control group, respectively. In the talazoparib group, the most common adverse events were anemia, fatigue, and decreased neutrophil count, and the most common event of grade 3 or higher was anemia, reported in 51% of the patients; two treatment-related deaths occurred.
Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.).
The New England journal of medicine. 2026 May 30 [Epub ahead of print]
Neeraj Agarwal, Nobuaki Matsubara, Arun A Azad, Fred Saad, Joaquin Mateo, Shusuan Jiang, Dingwei Ye, Eric Voog, Neal D Shore, Timuçin Çil, Christof Vulsteke, Hsiao-Jen Chung, Stefanie Zschäbitz, A Douglas Laird, Xiaoxi Zhang, Prachi Nandoskar, Sarah Fenech Chetcuti, Fong Wang, Karim Fizazi
Huntsman Cancer Institute, University of Utah, Salt Lake City., National Cancer Center Hospital East, Chiba, Japan., Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona., Hunan Cancer Hospital, Changsha, China., Fudan University Shanghai Cancer Center, Shanghai., Clinique Victor Hugo, Centre Jean Bernard, Le Mans, France., START Carolinas/Carolina Urologic Research Center, Myrtle Beach, SC., Adana City Education and Research Hospital, Adana Faculty of Medicine, University of Health Sciences, Adana, Turkey., Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, Belgium., Taipei Veterans General Hospital, Taipei, Taiwan., Department of Medical Oncology, Heidelberg University Hospital, and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany., Pfizer, South San Francisco, CA., Pfizer, New York., Pfizer, Berlin., Centre Oscar Lambret, University of Paris-Saclay, Lille, France.