As reported in The Lancet by Agarwal et al, the final overall survival analysis of the phase III TALAPRO-2 trial showed that the addition of talazoparib to enzalutamide resulted in a significant benefit in a cohort of patients with metastatic castration-resistant prostate cancer (CRPC) unselected for homologous recombination repair (HRR) gene alterations.
The primary analysis in this cohort showed that talazoparib plus enzalutamide significantly improved radiographic progression-free survival vs placebo plus enzalutamide in patients with metastatic CRPC unselected for HRR gene alterations.
Study Details
In the double-blind trial, 805 patients from sites in 26 countries with asymptomatic or mildly symptomatic disease and no prior life-prolonging therapy for CRPC were randomly assigned between January 2019 and September 2020 to receive talazoparib plus enzalutamide (n = 402) or placebo plus enzalutamide (n = 403). Patients received ongoing androgen-deprivation therapy. Overall survival was a key secondary endpoint.
Key Findings
Median follow-up was 52.5 months (interquartile range = 48.6–56.0 months).
Median overall survival was 45.8 months (95% confidence interval [CI] = 39.4–50.8 months) in the combination group vs 37.0 months (95% CI = 34.1–40.4 months) in the control group (hazard ratio [HR] = 0.80, 95% CI = 0.66–0.96, P = .016). Rates at 4 years were 48% vs 38%.
For the combination group vs the control group, the HR for overall survival among 169 HRR-deficient patients was 0.55 (95% CI = 0.36–0.83, P = .0035) and the HR among 636 HRR-nondeficient or unknown patients was 0.88 (95% CI = 0.71–1.08, P = .22).
With extended follow-up, median radiographic progression-free survival was 33.1 months in the combination group vs 19.5 months in the control group (HR = 0.67, 95% CI = 0.55–0.81, P < .0001).
The safety of talazoparib was consistent with its known profile. Overall, grade 3 or higher treatment-related adverse events occurred in 61% of the talazoparib plus enzalutamide group vs 19% of the control group; common events were anemia (49% vs 4%) and neutropenia (19% vs 1%). Discontinuation of talazoparib due to adverse events occurred in 22% of patients. Serious adverse events occurred in 46% vs 31% of patients. Treatment-related death occurred in one patient in the combination group and two patients in the control group.
The investigators concluded: “Combining talazoparib with enzalutamide significantly improved overall survival in patients with metastatic castration-resistant prostate cancer, supporting this combination as a standard-of-care initial treatment option for these patients.”
Neeraj Agarwal, MD, of Huntsman Cancer Institute, University of Utah, Salt Lake City, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Pfizer. For full disclosures of all study authors, visit thelancet.com.
