As reported at the 2026 ASCO Annual Meeting and in The New England Journal of Medicine by Agarwal et al, the phase III TALAPRO-3 trial has shown improved imaging-based progression-free survival with the addition of talazoparib to enzalutamide in patients receiving androgen-deprivation therapy for metastatic androgen pathway modulation–sensitive (APMS) prostate cancer harboring alterations in homologous recombination repair genes.
Study Details
In the international double-blind trial, 599 patients were randomly assigned between June 2021 and May 2023 to receive talazoparib at 0.5 mg (n = 300) or placebo (n = 299) once daily, both with enzalutamide at 160 mg once daily. The primary endpoint was investigator-assessed imaging-based progression-free survival.
Key Findings
Median follow-up for imaging-based progression-free survival was 38 months in both groups. At 3 years, progression-free survival was 77% (95% confidence interval [CI] = 71%–81%) in the talazoparib group vs 56% (95% CI = 50%–62%) in the control group (hazard ratio [HR] = 0.48, 95% CI = 0.36–0.65, P < .001).
Progression-free survival at 3 years was 77% vs 49% among patients with BRCA1 or BRCA2 alterations (HR = 0.37, 95% CI = 0.22–0.61) and 76% vs 60% among those without such alterations (HR = 0.57, 95% CI = 0.39–0.82).
Subsequent systemic anticancer treatment was received by 22% of the talazoparib group and 37% of the control group. At interim analysis for overall survival, 3-year overall survival was 78% in the talazoparib group vs 72% in the control group (HR = 0.77, 95% CI = 0.56–1.04).
Adverse events of grade 3 or higher were reported in 81% of the talazoparib group vs 44% of the control group; the most common included anemia (51%) and decreased neutrophils (11%) in the talazoparib group and hypertension (5%) and anemia (3%) in the control group. Serious adverse events occurred in 42% vs 32% of patients. Death considered related to treatment occurred in two patients in the talazoparib group (due to pancytopenia and worsening of idiopathic pulmonary fibrosis).
The investigators concluded: “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.”
Neeraj Agarwal, MD, of Huntsman Cancer Institute, University of Utah, Salt Lake City, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by Pfizer. For full disclosures of the study authors, visit nejm.org.
